AU2024332565A1

AU2024332565A1 - Lipidoid compounds and related compositions and uses

Info

Publication number: AU2024332565A1
Application number: AU2024332565A
Authority: AU
Inventors: Alicia M. DAVIS; Khalid A. HAJJ; Lijun Huang
Original assignee: Poseida Therapeutics Inc
Current assignee: Poseida Therapeutics Inc
Priority date: 2023-09-01
Filing date: 2024-08-30
Publication date: 2026-03-26
Also published as: IL326777A; MX2026002325A; WO2025049925A2; WO2025049925A3

Abstract

The present disclosure provides lipidoid compounds of formulae (I) and (II) and compositions comprising them, methods of preparing such compositions, and the use of these compositions in gene delivery applications.

Description

LIPIDOID COMPOUNDS AND RELATED COMPOSITIONS AND USES RELATED APPLICATIONS [0001] This application claims priority to, and the benefit of, U.S. Provisional Application No.63/580,080 filed on September 1, 2023, and U.S. Provisional Application No. 63/610,676, filed on December 15, 2023. The contents of each of the aforementioned patent applications are incorporated herein by reference in their entireties. SEQUENCE LISTING [0002] The Sequence Listing XML associated with this application is provided electronically in XML format and is hereby incorporated by reference into the specification. The name of the XML file containing the Sequence Listing XML is “POTH-088_001WO_SeqList.xml”. The XML file is 25,048 bytes, created on August 29, 2024, and is being submitted electronically via USPTO Patent Center. FIELD [0003] The present invention relates generally to lipidoid compounds, compositions containing such compounds, methods of preparing these compounds, and the use of these compositions in gene delivery. BACKGROUND [0004] There has been a long-felt but unmet need in the art for compositions and methods for delivering nucleic acids to cells and for genetically modifying cells in vivo, ex vivo and in vitro. Widely accepted gene delivery and genetic modification techniques, such as the use of viral vectors, including AAVs, can cause acute toxicity and harmful side-effects in patients. The present disclosure provides improved compositions, methods and kits for the delivery of nucleic acids to various types of cells, including hepatocytes, in vivo, ex vivo and in vitro. More specifically, the present disclosure provides improved lipid nanoparticle compositions and methods of using the same. These lipid nanoparticle compositions and methods allow for the delivery of nucleic acids to cells with high efficiency and low toxicity. Thus, the compositions and methods of the present disclosure have wide applicability to a diverse number of fields, including gene therapy. SUMMARY [0005] In some aspects, provided are novel compounds. In one aspect, the novel compound is a compound of Formula (I): [0006] Formula (I) or a salt thereof, wherein: covalent bond; each of Xa, Xb and Xc is independently NH or O; each of Y_a, Y_b, Y_c, Y_d, Y_e and Y_f is independently C or O; each of r, s and t is independently an integer ranging from 1 to 9; and each of R2a, R2b, R2c, R2d, R2e, and R2f is independently C1-C18 alkyl, C2-C18 alkenyl, - (cyclohexyl)-(C₁-C₁₈ alkyl), -(cyclohexyl)-(C₂-C₁₈ alkenyl), or -(cyclohexyl)-(CH₂-O-CO)- (C₁-C₁₈ alkyl), wherein the C₁-C₁₈ alkyl or C₂-C₁₈ alkenyl is optionally substituted with one or more cyclohexyl. [0007] In another aspect, the novel compound is a compound of Formula (II): Formula (II) or a salt thereof, wherein: each of Y_a, Y_b, Y_c and Y_d is independently C or O; each of r and s is independently an integer ranging from 1 to 9; R₁ is H or C1-C3 alkyl; and each of R_2a, R_2b, R_2c, and R_2d is independently C₁-C₁₈ alkyl or C₂-C₁₈ alkenyl, -(cyclohexyl)- (C1-C18 alkyl), -(cyclohexyl)-(C2-C18 alkenyl), or -(cyclohexyl)-(CH2-O-CO)-(C1-C18 alkyl), wherein the C1-C18 alkyl or C2-C18 alkenyl is optionally substituted with one or more cyclohexyl. [0008] In some aspects, provided are novel lipid nanoparticles (“LNPs”) comprising a novel compound. In one aspect, the novel compound is a compound of Formula (I). In another aspect, the novel compound is a compound of Formula (II). In another aspect, the novel compound is a compound of Formula (II’). [0009] In some aspects, provided are pharmaceutical compositions, comprising a composition of the present disclosure and at least one pharmaceutically-acceptable excipient or diluent. [0010] In some aspects, provided are methods of delivering at least one nucleic acid to at least one cell comprising contacting the at least one cell with at least one composition of the present disclosure. [0011] In some aspects, provided are methods of genetically modifying at least one cell comprising contacting the at least one cell with at least one composition of the present disclosure. [0012] In some aspects, provided are methods of treating at least one disease or disorder in a subject in need thereof comprising administering to the subject at least one therapeutically effective amount of at least one composition of the present disclosure. [0013] In some aspects, provided are methods of delivering at least one nucleic acid to at least one cell comprising contacting the at least one cell with at least one composition of the present disclosure. [0014] In some aspects, provided are cells modified according to methods of the present disclosure. [0015] Any of the aspects and/or embodiments described herein can be combined with any other aspect and/or embodiment described herein. [0016] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the Specification, the singular forms also include the plural unless the context clearly dictates otherwise; as examples, the terms “a,” “an,” and “the” are understood to be singular or plural and the term “or” is understood to be inclusive. By way of example, “an element” means one or more element. Throughout the specification the word “comprising,” or variations such as “comprises” or “comprising,” will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. About can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from the context, all numerical values provided herein are modified by the term “about.” [0017] Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. The references cited herein are not admitted to be prior art to the claimed invention. In the case of conflict, the present Specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. Other features and advantages of the disclosure will be apparent from the following detailed description and claim. DETAILED DESCRIPTION [0018] The present disclosure provides novel lipidoid compounds, novel lipid nanoparticle compositions (LNPs) comprising the novel lipidoid compounds, methods for preparing the LNPs, and methods for using same. In a non-limiting example, the compositions and methods of the present limiting disclosure can be used for gene delivery. In a non-limiting example, the compositions and methods of the present disclosure can be broadly used to deliver a nucleic acid to liver cells, in vivo, ex vivo or in vitro, for the treatment of certain diseases and disorders, including, but not limited to liver disorders. In a non-limiting example, the compositions and methods of the present disclosure can be broadly used to deliver a nucleic acid to induce the expression of a secreted therapeutic protein. Compounds of the Present Disclosure [0019] In one aspect, the present disclosure provides compounds of Formula (I): Formula (I) or a salt thereof, wherein: covalent bond; each of X_a, X_b and X_c is independently NH or O; each of Y_a, Y_b, Y_c, Y_d, Y_e and Y_f is independently C or O; each of r, s and t is independently an integer ranging from 1 to 9; and each of R_2a, R_2b, R_2c, R_2d, R_2e, and R_2f is independently C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, - (cyclohexyl)-(C₁-C₁₈ alkyl), -(cyclohexyl)-(C₂-C₁₈ alkenyl), or -(cyclohexyl)-(CH₂-O-CO)- (C1-C18 alkyl), wherein the C1-C18 alkyl or C2-C18 alkenyl is optionally substituted with one or more cyclohexyl. [0020] In some aspects, the novel compound is a compound of Formula (I): Formula (I) or a salt thereof, wherein: covalent bond; each of Xa and Xb is independently NH or O; each of Y_a, Y_b, Y_c, and Y_d is independently C or O; each of r and s is independently an integer ranging from 1 to 9; and each of R2a, R2b, R2c, and R2d is independently C1-C18 alkyl, C2-C18 alkenyl, -(cyclohexyl)-(C1- C₁₈ alkyl), or -(cyclohexyl)-(C₂-C₁₈ alkenyl), wherein the C₁-C₁₈ alkyl or C₂-C₁₈ alkenyl is optionally substituted with one or more cyclohexyl. [0022] In some aspects, . [0025] In some aspects, . [0026] In some aspects, Z is a covalent bond. [0027] In some aspects, each of Xa, Xb and Xc is NH. [0028] In some aspects, each of X_a, X_b and X_c is O. [0029] In some aspects, each of Y_a, Y_b, Y_c, Y_d, Y_e and Y_f is C. [0030] In some aspects, each of Ya, Yb, Yc, Yd, Ye and Yf is O. [0031] In some aspects, each of r, s, and t is 3. [0032] In some aspects, each of R_2a, R_2b, R_2c, R_2d, R_2e, and R_2f is C₁-C₁₈ alkyl. [0033] In some aspects, each of Xa and Xb is NH. [0034] In some aspects, each of Xa and Xb is O. [0035] In some aspects, each of Y_a, Y_b, Y_c, and Y_d is C. [0036] In some aspects, each of Y_a, Y_b, Y_c, and Y_d is O. [0037] In some aspects, each of r and s is 3. [0038] In some aspects, each of R_2a, R_2b, R_2c, and R_2d is C₁-C₁₈ alkyl. [0039] In some aspects, each of R_2a, R_2b, R_2c, and R_2d is C₁-C₁₈ alkyl substituted with one or more cyclohexyl. In some embodiments, each of R2a, R2b, R2c, and R2d is . [0040] In some aspects, each of R2a, R2b, R2c, and R2d is -(cyclohexyl)-(C1-C18 alkyl). In some embodiments, each [0041] In some aspects, each of R_2a, R_2b, R_2c, R_2d, R_2e, and R_2f is -(cyclohexyl)-(CH₂-O-CO)- (C₁-C₁₈ alkyl). [0042] In some aspects, Z is and each of X_a and X_b is NH. In some embodiments, each of Ya, Yb, Yc and Yd is C. In some embodiments, each of Ya, Yb, Yc and Y_d is O. In some embodiments, each of r and s is 3. In some embodiments, each of R_2a, R_2b, R_2c, and R_2d is C₁-C₁₈ alkyl. In some embodiments, each of R_2a, R_2b, R_2c, and R_2d is C₁-C₁₈ alkyl substituted with one or more cyclohexyl. In some embodiments, each of R2a, R2b, R2c, [0043] In some aspects, Z is and each of X_a and X_b is O. In some embodiments, each of Ya, Yb, Yc and Yd is C. In some embodiments, each of Ya, Yb, Yc and Y_d is O. In some embodiments, each of r and s is 3. In some embodiments, each of R_2a, R_2b, R2c, and R2d is C1-C18 alkyl. In some embodiments, each of R2a, R2b, R2c, and R2d is C1-C18 alkyl substituted with one or more cyclohexyl. In some embodiments, each of R2a, R2b, R2c, . [0044] In some aspects, Z is a covalent bond and each of X_a and X_b is O. In some embodiments, each of Y_a, Y_b, Y_c and Y_d is C. In some embodiments, each of Y_a, Y_b, Y_c and Yd is O. In some embodiments, each of r and s is 3. In some embodiments, each of R2a, R2b, R2c, and R2d is C1-C18 alkyl. In some embodiments, each of R2a, R2b, R2c, and R2d is C1-C18 alkyl substituted with one or more cyclohexyl. In some embodiments, each of R_2a, R_2b, R_2c, [0045] In some aspects, Z is and each of Xa and Xb is NH. In some embodiments, each of Ya, Yb, Yc and Yd is C. In some embodiments, each of Ya, Yb, Yc and Y_d is O. In some embodiments, each of r and s is 3. In some embodiments, each of R_2a, R_2b, R_2c, and R_2d is C₁-C₁₈ alkyl. In some embodiments, each of R_2a, R_2b, R_2c, and R_2d is C₁-C₁₈ alkyl substituted with one or more cyclohexyl. In some embodiments, each of R2a, R2b, R2c, . [0046] In some aspects, each of X_a and X_b is NH. In some embodiments, each of Ya, Yb, Yc, Yd, Ye and Yf is C. In some embodiments, each of r, s, and t is 3. In some embodiments, each of R2a, R2b, R2c, R2d, R2e, and R2f is C1-C18 alkyl. [0047] In some aspects, each of Xa, Xb, and Xc is NH. In some embodiments, each of Ya, Yb, Yc, Yd, Ye and Yf is C. In some embodiments, each of r, s, and t is 3. In some embodiments, each of R_2a, R_2b, R_2c, R_2d, R2e, and R2f is C1-C18 alkyl. [0048] In some aspects, each of Xa and Xb, is O. In some embodiments, each of Y_a, Y_b, Y_c, and Y_d is C. In some embodiments, each of r and s is 3. In some embodiments, each of R2a, R2b, R2c, and R2d is C1-C18 alkyl. [0049] In some aspects, the compound of Formula (I) is a compound selected from: , [0050] In one aspect, the present disclosure provides compounds of Formula (II): Formula (II) or a salt thereof, wherein: G is each of Y_a, Y_b, Y_c and Y_d is independently C or O; each of r and s is independently an integer ranging from 1 to 9; R₁ is H or C₁-C₃ alkyl; and each of R_2a, R_2b, R_2c, and R_2d is independently C₁-C₁₈ alkyl, C₂-C₁₈ alkenyl, -(cyclohexyl)-(C₁- C18 alkyl), -(cyclohexyl)-(C2-C18 alkenyl), or -(cyclohexyl)-(CH2-O-CO)-(C1-C18 alkyl), wherein the C1-C18 alkyl or C2-C18 alkenyl is optionally substituted with one or more cyclohexyl. [0051] In one aspect, the present disclosure provides a compound of Formula (II’): Formula (II’) or a salt thereof, wherein: each of Ya, Yb, Yc and Yd is independently C or O; each of r and s is independently an integer ranging from 1 to 9; R1 is H or C1-C3 alkyl; and each of R_2a, R_2b, R_2c, and R_2d is independently C₁-C₁₈ alkyl or C₂-C₁₈ alkenyl, wherein the C₁- C18 alkyl or C2-C18 alkenyl is optionally substituted with one or more cyclohexyl. [0052] In some aspects, [0053] In some aspects, [0054] In some aspects, [0055] In some aspects, each of Ya, Yb, Yc and Yd is C. [0056] In some aspects, each of Y_a, Y_b, Y_c and Y_d is O. [0057] In some aspects, each of r and s is 3. [0058] In some aspects, R1 is H. [0059] In some aspects, each of R_2a, R_2b, R_2c, and R_2d is C₁-C₁₈ alkyl. [0060] In some aspects, each of R_2a, R_2b, R_2c, and R_2d is C₁-C₁₈ alkyl substituted with one or more cyclohexyl. In some embodiments, each of R2a, R2b, R2c, and R2d is . [0061] In some aspects, each of R2a, R2b, R2c, and R2d is -(cyclohexyl)-(CH2-O-CO)-(C1-C18 alkyl). [0062] In some aspects, the compound of Formula (II) or Formula (II’) is a compound selected from: , . [0063] It will be understood that the compounds of any one of the Formulas disclosed herein and any pharmaceutically acceptable salts thereof, comprise stereoisomers, mixtures of stereoisomers, polymorphs of all isomeric forms of said compounds. [0064] It will be understood that while compounds disclosed herein may be presented without specified configuration (e.g., without specified stereochemistry). Such presentation intends to encompass all available isomers, tautomers, regioisomers, and stereoisomers of the compound. In some embodiments, the presentation of a compound herein without specified configuration intends to refer to each of the available isomers, tautomers, regioisomers, and stereoisomers of the compound, or any mixture thereof. [0065] It is to be understood that the compounds of any Formula described herein include the compounds themselves, as well as their salts, and their solvates, if applicable. A salt, for example, can be formed between an anion and a positively charged group (e.g., amino) on a substituted compound disclosed herein. Suitable anions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate, tartrate, tosylate, salicylate, lactate, naphthalenesulfonate, and acetate (e.g., trifluoroacetate). [0066] It will be understood that in any of the formulae described herein, when a “ ” is used to indicate linkage between two variables (e.g., A-B), the linkage could be one or more covalent bonds. General Methods for the Preparation of Compounds of Formula (I), Formula (II), or Formula (II’) of the Present Disclosure [0067] Compounds of Formula (I), Formula (II), or Formula (II’) can be prepared using the reagents, intermediates, precursors, methods and schemes disclosed herein or using other commercially available reagents and methods known to those skilled in the art. General Procedure for Synthesis of Lipidoids (A) [0068] To a solution of N-Boc Pentanoic acid 1 (10g, 46 mmol) and N-Boc 1,4-Diamine 2 (8.66 g, 1.0 eq) in dry dichloromethane (DCM, 200 ml) was added 1-Ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDCI, 10.6 g, 1.2 eq), N,N-Diisopropylethylamine (DIEA, 12.7 ml, 1.5 eq) and 4-dimethylaminopyridine (DMAP, 280 mg, cat.) sequentially at room temperature. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was then quenched with saturated NaHCO3 (150 ml) and extracted with DCM three times to get crude product, which was recrystallized with 10 MeOH in DCM to get white solid (13 g, 75% yield). [0069] The Boc protected Diamine 3 (2 g) was dissolved in 2 ml DCM followed by addition of 2 ml TFA at room temperature. The resulting reaction mixture was stirred at room temperature for 1-2 hrs until TLC showed no starting material remaining, and then the bottom layer was separated out to give crude diamine TFA salt after stripping the remaining trace amount of TFA (3 g). [0070] Crude diamine (500 mg, contained TFA) was mixed with R-substituted epoxide 5 (4.0 eq) in the presence of 2.0 eq Cs2CO3. The suspension was heated to 78^oC for 48 hrs. The residue was applied to a silica gel column to get desired product 6 in clear oil (yield around 35%). General Procedure for Synthesis of Lipidoids (B) [0071] Intermediate 8 [0072] A mixture of 1,2-epoxydodecane (5g, 27.2 mmol) and N-Boc 1,4 diamine (2.55 g, 0.5 eq) was heated to 80^oC overnight. After both LCMS and TLC showed the reaction was completed, the reaction mixture was re-dissolved in 50% trifluoroacetic acid (TFA) in DCM (20 ml) and the resulting reaction mixture was stirred at room temperature for 2-3 hours until the starting material disappeared. The solvent was stripped off, followed by extraction with DCM and sat NaHCO₃ to give the crude product, which was applied to next step without further purification. [0073] Intermediate 10 [0074] To a mixture of disulfide acid 9 (500mg, 2.1 mmol) and N-OH Succinimide (289mg, 2.4 eq) in dry DCM (20 ml) was added sequentially EDCI (1.05g, 2.6 eq), DIEA (812mg, 3.0eq) and cat DMAP (25mg) at room temperature. The resulting reaction mixture was stirred at room temperature for 24 hrs and quenched with sat NaHCO3 (20 ml), followed by stripping of the solvent and extraction with DCM and brine to provide crude product. The residue was applied to the next step without further purification. [0075] Intermediate 15 or 16 [0076] The cyclohexyl alcohol 13 or 14 was mixed with solid NaOH (2.0 eq) and the resulting suspension was heated to 45^oC for 30 mins followed by addition of tetrabutylammonium bromide (0.05 eq) and epichlorohydrin (2.0 eq). The reaction suspension was vigorously stirred at 50^oC for 24 hrs. The reaction mixture was cooled down and the residue was extracted with cold EtOAc and H₂O. After drying over Na₂SO₄, the crude product was purified by flash column to get desired product 15 or 16 in 76% yield. [0077] Intermediate 18 [0078] Diol 17 was mixed with succinic anhydride (2.1 eq) in DCM followed by treatment with DMAP (2.1 eq) at room temperature. The resulting reaction mixture was stirred for 18 hrs and EDCI (2.3 eq), DMAP (2.3 eq) and N-OH succinate (2.1 eq) were added sequentially. The reaction mixture was stirred at room temperature overnight. The reaction was quenched with sat NaHCO3 and extracted with DCM three times. The combined organic layer was concentrated after drying to afford the crude product, which was purified by silica gel flash chromograph to provide desired Bis-NHS ester 18 in 45% yield. [0079] Compound 1 [0080] To a solution of crude NHS ester 10 (100mg, 0.23mmol) in dry THF (5ml) was added the intermediate 8 (313 mg, 3.0 eq) and DIEA (127 uL, 3.0 eq). The resulting reaction mixture was stirred at room temperature for 24 hrs. After the solvent was stripped, the residue was applied to a silica gel column to get desired product Compound 1 (105 mg, 41% yield) as a clear oil. [0081] ¹H NMR (500 MHz, CDCl3) δ 7.26 (br, 1H), 7.13 (br, 1H), 4.01 – 3.84 (m, 4H), 3.32- 3.25 (m, 6H), 3.13-3.05 (m, 6H), 2.94-2.93 (m,4H), 2.74-2.69 (m, 4H), 2.37-2.34 (m, 4H), 2.05-1.99 (m, 4H), 1.82-1.80 (m, 4H), 1.62-1.37 (m, 20H), 1.34-1.20 (m, 62H), 0.88 (t, J=10Hz, 12H). MS (ESI): calcd. for C₆₄H₁₃₀N₄O₆S₂ [M+H]⁺ 1114.9, found 1116.3. [0083] A mixture of 1,2-epoxydodecane (500mg, 2.7mmol) and 4-OH Butylamine (120 mg, 0.5 eq) was heated to 80^oC overnight to get intermediate 12. After both LCMS and TLC showed the reaction was complete, the reaction mixture was re-dissolved in dry DCM (100 ml) followed by sequential addition of disulfide acid 9 (385mg, 0.6 eq), EDCI (674mg, 1.3eq), and DIEA (0.75ml, 1.5 eq). The resulting reaction mixture was stirred at room temperature for 24 hours until the starting material disappeared. The reaction mixture was quenched with sat NaHCO3 and extracted with DCM to get crude product after the solvent was stripped off, which was then applied to silica gel purification. [0084] ¹H NMR (500 MHz, CDCl3) δ 4.11 – 4.09 (m, 4H), 3.62-3.60 (m, 4H),2.62(s, 4H), 2.59-2.53 (m,6H), 2.42-2.37 (m, 6H), 1.63-1.53 (m, 6H), 1.51-1.45 (m, 6H), 1.44-1.40 (m, 4H), 1.39-1.36 (m, 8H), 1.33-1.25 (m, 68H), 0.88 (t, J=10Hz, 12H). MS (ESI): calcd. for C64H128N2O8S2 [M+H]⁺ 1116.9, found 1118.2. [0085] Compound 3 [0086] A mixture of tri-ol 12 (300mg, 0.656 mmol) and succinic anhydride (72mg, 1.1 eq) in dry DCM (5 ml) was treated with DIEA (151 ul, 1.2 eq) at room temperature overnight. To the resulting reaction mixture was added sequentially EDCI (163mg, 1.3 eq), another 0.9 eq of 12 (270mg), DIEPA (150 uL, 1.2 eq) and cat. DMAP. The reaction mixture was stirred for 24 hrs followed by silica gel chromatography purification to give desired product Compound 3 as colorless oil (108 mg, 17%). [0087] ¹H NMR (500 MHz, CDCl3) δ 4.09 – 4.07 (m, 4H), 3.62-3.60 (m, 4H),2.73-2.70(t, J=10Hz, 4H), 2.59-2.53 (m, 4H), 2.45-2.38 (m, 10H), 2.04-2.0 (m, 4H), 1.65-1.40 (m, 14H), 1.33-1.25 (m, 64H), 0.88 (t, J=10Hz, 12H). MS (ESI): calcd. for C60H120N2O8 [M+H]⁺ 996.9, found 998.1.

General Procedure for Synthesis of Lipidoids (C)

[0088] Intermediate 20 [0089] Following the similar procedure of intermediate 18, intermediate 20 was obtained in 41% yield as an off white solid, and was then treated with diamine intermediate 8 in DMF in the presence of TEA at room temperature. The crude product was obtained after workup and extraction with DCM/sat NaHCO3. The silica gel chromatography provided oil like desired Compound 17 in 28% yield. [0090] Intermediate 21 [0091] To a solution of intermediate 8 in dry DCM (0.5 M) was added acryl chloride (6 eq) drop wise in the presence of DIEA (10 eq) in an ice bath. The resulting reaction mixture was stirred at room temperature overnight and quenched with sat. NaHCO3 followed by extraction with DCM. After concentration the crude product was treated with 3 N NaHCO₃ in a mixture of solvents MeOH/H2O until most of the starting material disappeared. The resulting reaction mixture was neutralized with HCl and extracted with DCM to get desired intermediate 21 after purification by silica gel chromatography in 67% yield. [0092] Compound 16 [0093] A neat mixture of intermediate 21 (2.2 eq) with intermediate 8 was heated to 90^oC in a sealed tube for 48 hrs. Compound 16 was purified by silica gel in 35% yield. [0094] Compound 19 [0095] Following the similar procedure of intermediate 20, DMF was used as the solvent for the preparation of intermediate 23, which was directly applied to the next ester formation without further separation by using EDCI as a coupling reagent in the presence of DMAP. Compound 19 was obtained in 15% yield over two steps. General Procedure for Synthesis of Lipidoids (D) [0096] Intermediate 25 [0097] A neat reaction of a solution of starting material 24 with 2.0 eq powder NaOH was heated at 50^oC for 1 hr and then epichlorohydrin (2.0 eq) and cat. tetrabutylammonium bromide (TBAB) were added (2.0 eq). The resulting reaction mixture was stirred at the same temperature overnight. The reaction mixture was diluted with DCM followed by filtration via celite pad to get crude intermediate 25, which was purified by silica gel chromatography in 56% yield. [0098] Intermediate 27 [0099] Intermediate 25 was treated with camphorsulfonic acid (CSA, 0.1 eq) in a mixture of solvents DCM and MeOH (1/1) for 24 hrs and then neutralized and concentrated to get crude product, which was purified by chromatography to get desired alcohol 26. The coupling of 26 with hexanoic acid was executed by following the standard protocol using EDCI, DMAP in DCM. ¹H NMR (500 MHz, CDCl3) δ 4.00-3.98 (d, J=10 Hz, 1H), 3.89-3.88 (d, J=5Hz, 1H), 3.72-3.69 (m, 1H), 3.43-3.27 (m, 3H), 3.15-3.12 (m, 1H), 2.79 (t, J=5Hz, 1H), 2.61-2.59 (dd, J=5Hz, 10Hz, 1H), 2.29 (t, 5Hz, 2H), 1.85-1.78 (m, 3H), 1.65-1.50 (m, 6H), 1.43-1.27 (m, 5H), 1.01-0.95 (m, 2H), 0.89 (t, J=5Hz, 3H). MS (ESI): calcd. for C17H30O4 [M+Na]⁺ 321.2, found 321.1. [0100] Intermediates 30 and 31 [0101] A starting amine and intermediate 27 (2.2eq) were combined and the neat reaction heated at 85^o-90^oC for 24-48 hrs to get desired diol 28 or 29 in 30-40% yields after chromatography purification. The diol was treated with TFA (5.0 eq) in DCM for 2-3 hrs at room temperature to provide amine 30 and acid 31 after purification by silica gel chromatography. [0102] Compound 20 [0103] Acid 31 was mixed with EDCI and alcohol in DCM and stirred at room temperature for 30 mins in the presence of molecular sieves and then amine 30 and DIEA were added via syringe. The resulting reaction mixture was kept stirring for 8 hrs and worked-up with a standard protocol. After purification by chromatography, Compound 20 was obtained in 45% yield. General Procedure for Synthesis of Lipidoids (E) General Scheme E [0104] Intermediate 34 [0105] A mixture of azido-Butanol (1.1 g) with Octyl aldehyde (0.3 eq, 500 mg) was heated at 110^oC for 5 hrs and purified by silica gel to get desired product di-N3 C10 (510 mg, 43%), which was then treated with Pd-C in methanol for 48 hrs to give diamine 34 in the presence of an H2 ballon.¹H NMR (500 MHz, CDCl3) δ 4.45 (t, J=5 Hz, 1H), 3.60-3.58 (m, 2H), 3.44- 3.41 (m, 2H), 2.74 (m, 4H), 1.98-1.95 (m, 8H), 1.63-1.52 (m, 6H), 1.29-1.26 (m, 14H), 0.89 (t, J=5Hz, 3H). [0106] Compound 21 [0107] The diamine 34 was reacted with epoxide at 88^oC for 24 hrs to afford Compound 21 in 35% yield after silica gel chromatography purification. [0108] Intermediate 37 [0109] To a solution of 4-OH 1-Boc Butylamine (189 mg, 1 mmol) in acetonitrile (5 mL) was added pyridine (240 uL, 3 mmol) and 4-nitrophenyl chloroformate (280 mg, 1.4 mmol) at room temperature. Upon stirring for 4 h, 4-NH21-Boc Butylamine (380 mg, 2 mmol) was added, and the resulting reaction mixture was stirred an additional 2 h. The reaction mixture was extracted into DCM (50 mL), washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude residue was purified using silica gel chromatography (10% EtOAc in hexanes) to provide intermediate 37 (141 mg) 35% yield) as a clear oil.¹H NMR (500 MHz, CDCl3) δ 4.07-4.04 (m, 2H), 3.19-2.89(m, 6H), 1.63-1.51 (m, 8H), 1.44 (s, 18H). MS (ESI): calcd. for C₁₉H₃₇N₃O₆ [M+H]⁺ 404.3, found 404.1 [0110] Compound 22 [0111] Carbamate Diamine 37 was re-dissolved in DCM followed by treatment with 4 N HCl in Dioxane (10 eq) and stirred at room temperature overnight to get diamine 38 HCl salt in white solid after removal of solvent. The diamine was heated with 1,2 epoxy dodecane by following a standard epoxide ring opening protocol to get Compound 22 in 31% yield after column purification. Lipid Nanoparticles of the Present Disclosure [0112] The present disclosure provides lipid nanoparticles (LNPs) comprising one or more compounds of Formula (I), Formula (II’), and/or Formula (II). In addition to the one or more compounds of Formula (I), Formula (II’), and/or Formula (II), the LNPs of the present disclosure can comprise one or more additional LNP components, as described below. [0113] In some aspects, an LNP of the present disclosure can comprise at least about 2.5%, or at least about 5%, or at least about 7.5%, or at least about 10%, or at least about 12.5%, or at least about 15%, or at least about 17.5%, or at least about 20%, or at least about 22.5%, or at least about 25%, or at least about 27.5%, or at least about 30%, or at least about 32.5%, or at least about 35%, or at least about 37.5%, or at least about 40%, or at least about 42.5%, or at least about 45%, or at least about 47.5%, or at least about 50%, or at least about 52.5%, or at least about 55%, or at least about 57.5% or at least about 60%, or at least about 62.5%, or at least about 65%, or at least about 67.5%, or at least about 70% of at least one compound of the present disclosure by moles. In some aspects, the at least one compound is at least one compound of Formula (I), Formula (II’), or Formula (II), as described herein. In some aspects, the at least one compound of the present disclosure is a mixture of two or more compounds of Formula (I), Formula (II’), or Formula (II). [0114] In some aspects, an LNP of the present disclosure can comprise about 2.5%, or about 5%, or about 7.5%, or about 10%, or about 12.5%, or about 15%, or about 17.5%, or about 20%, or about 22.5%, or about 25%, or about 27.5%, or about 30%, or about 32.5%, or about 35%, or about 37.5%, or about 40%, or about 42.5%, or about 45%, or about 47.5%, or about 50%, or about 52.5%, or about 55%, or about 57.5% or about 60%, or about 62.5%, or about 65%, or about 67.5%, or about 70% of at least one compound of the present disclosure by moles. In some aspects, the at least one compound is at least one compound of Formula (I), Formula (II’), or Formula (II), as described herein. In some aspects, the at least one compound of the present disclosure is a mixture of two or more compounds of Formula (I), Formula (II’), or Formula (II). [0115] Structural Lipid [0116] In some aspects, an LNP can further comprise at least about 2.5%, or at least about 5%, or at least about 7.5%, or at least about 10%, or at least about 12.5%, or at least about 15%, or at least about 17.5%, or at least about 20%, or at least about 22.5%, or at least about 25%, or at least about 27.5%, or at least about 30%, or at least about 32.5%, or at least about 35%, or at least about 37.5%, or at least about 40%, or at least about 42.5%, or at least about 45%, or at least about 47.5%, or at least about 50%, or at least about 52.5%, or at least about 55%, or at least about 57.5% or at least about 60%, or at least about 62.5%, or at least about 65%, or at least about 67.5%, or at least about 70% of at least one structural lipid by moles. [0117] In some aspects, a structural lipid can be a steroid. In some aspects, a structural lipid can be a sterol. In some aspects, a structural lipid can comprise cholesterol. In some aspects, a structural lipid can comprise ergosterol. In some aspects, a structural lipid can be a phytosterol. [0118] In some aspects, the at least one structural lipid is a mixture of two structural lipids. [0119] Phospholipid [0120] In some aspects, an LNP can further comprise at least about 2.5%, or at least about 5%, or at least about 7.5%, or at least about 10%, or at least about 12.5%, or at least about 15%, or at least about 17.5%, or at least about 20%, or at least about 22.5%, or at least about 25%, or at least about 27.5%, or at least about 30%, or at least about 32.5%, or at least about 35%, or at least about 37.5%, or at least about 40%, or at least about 42.5%, or at least about 45%, or at least about 47.5%, or at least about 50%, or at least about 52.5%, or at least about 55%, or at least about 57.5% or at least about 60%, or at least about 62.5%, or at least about 65%, or at least about 67.5%, or at least about 70% of at least one phospholipid by moles. [0121] As used herein, the term “phospholipid” is used in its broadest sent to refer to any amphiphilic molecule that comprises a polar (hydrophilic) headgroup comprising phosphate and two hydrophobic fatty acid chains. In some aspects, a phospholipid can comprise dioleoylphosphatidylethanolamine (DOPE). In some aspects, a phospholipid can comprise 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC). In some aspects, a phospholipid can comprise 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC). In some aspects, a phospholipid can comprise DDPC (1,2-Didecanoyl-sn-glycero-3-phosphocholine), DEPA- NA (1,2-Dierucoyl-sn-glycero-3-phosphate (Sodium Salt)), DEPC (1,2-Dierucoyl-sn- glycero-3-phosphocholine), DEPE (1,2-Dierucoyl-sn-glycero-3-phosphoethanolamine), DEPG-NA (1,2-Dierucoyl-sn-glycero-3[Phospho-rac-(1-glycerol) (Sodium Salt)), DLOPC (1,2-Dilinoleoyl-sn-glycero-3-phosphocholine), DLPA-NA (1,2-Dilauroyl-sn-glycero-3- phosphate (Sodium Salt)), DLPC (1,2-Dilauroyl-sn-glycero-3-phosphocholine), DLPE (1,2- Dilauroyl-sn-glycero-3-phosphoethanolamine), DLPG-NA (1,2-Dilauroyl-sn-glycero- 3[Phospho-rac-(1-glycerol) (Sodium Salt)), DLPG-NH4 (1,2-Dilauroyl-sn-glycero- 3[Phospho-rac-(1-glycerol) (Ammonium Salt)), DLPS-NA (1,2-Dilauroyl-sn-glycero-3- phosphoserine (Sodium Salt)), DMPA-NA (1,2-Dimyristoyl-sn-glycero-3-phosphate (Sodium Salt)), DMPC (1,2-Dimyristoyl-sn-glycero-3-phosphocholine), DMPE (1,2-Dimyristoyl-sn- glycero-3-phosphoethanolamine), DMPG-NA (1,2-Dimyristoyl-sn-glycero-3[Phospho-rac- (1-glycerol) (Sodium Salt)), DMPG-NH4 (1,2-Dimyristoyl-sn-glycero-3[Phospho-rac-(1- glycerol) (Ammonium Salt)), DMPG-NH4/NA (1,2-Dimyristoyl-sn-glycero-3[Phospho-rac- (1-glycerol) (Sodium/Ammonium Salt)), DMPS-NA (1,2-Dimyristoyl-sn-glycero-3- phosphoserine (Sodium Salt)), DOPA-NA (1,2-Dioleoyl-sn-glycero-3-phosphate (Sodium Salt)), DOPC (1,2-Dioleoyl-sn-glycero-3-phosphocholine), DOPE (1,2-Dioleoyl-sn-glycero- 3-phosphoethanolamine), DOPG-NA (1,2-Dioleoyl-sn-glycero-3[Phospho-rac-(1-glycerol) (Sodium Salt)), DOPS-NA (1,2-Dioleoyl-sn-glycero-3-phosphoserine (Sodium Salt)), DPPA- NA (1,2-Dipalmitoyl-sn-glycero-3-phosphate (Sodium Salt)), DPPC (1,2-Dipalmitoyl-sn- glycero-3-phosphocholine), DPPE (1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine), DPPG-NA (1,2-Dipalmitoyl-sn-glycero-3[Phospho-rac-(1-glycerol) (Sodium Salt)), DPPG- NH4 (1,2-Dipalmitoyl-sn-glycero-3[Phospho-rac-(1-glycerol) (Ammonium Salt)), DPPS-NA (1,2-Dipalmitoyl-sn-glycero-3-phosphoserine (Sodium Salt)), DSPA-NA (1,2-Distearoyl-sn- glycero-3-phosphate (Sodium Salt)), DSPC (1,2-Distearoyl-sn-glycero-3-phosphocholine), DSPE (1,2-Distearoyl-sn-glycero-3-phosphoethanolamine), DSPG-NA (1,2-Distearoyl-sn- glycero-3[Phospho-rac-(1-glycerol) (Sodium Salt)), DSPG-NH4 (1,2-Distearoyl-sn-glycero- 3[Phospho-rac-(1-glycerol) (Ammonium Salt)), DSPS-NA (1,2-Distearoyl-sn-glycero-3- phosphoserine (Sodium Salt)), EPC (Egg-PC), HEPC (Hydrogenated Egg PC), HSPC (Hydrogenated Soy PC), LYSOPC MYRISTIC (1-Myristoyl-sn-glycero-3-phosphocholine), LYSOPC PALMITIC (1-Palmitoyl-sn-glycero-3-phosphocholine), LYSOPC STEARIC (1- Stearoyl-sn-glycero-3-phosphocholine), Milk Sphingomyelin (MPPC; 1-Myristoyl-2- palmitoyl-sn-glycero 3-phosphocholine), MSPC (1-Myristoyl-2-stearoyl-sn-glycero-3– phosphocholine), PMPC (1-Palmitoyl-2-myristoyl-sn-glycero-3–phosphocholine), POPC (1- Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), POPE (1-Palmitoyl-2-oleoyl-sn-glycero-3- phosphoethanolamine), POPG-NA (1-Palmitoyl-2-oleoyl-sn-glycero-3[Phospho-rac-(1- glycerol)] (Sodium Salt)), PSPC (1-Palmitoyl-2-stearoyl-sn-glycero-3–phosphocholine), SMPC (1-Stearoyl-2-myristoyl-sn-glycero-3–phosphocholine), SOPC (1-Stearoyl-2-oleoyl- sn-glycero-3-phosphocholine), SPPC (1-Stearoyl-2-palmitoyl-sn-glycero-3-phosphocholine), or any combination thereof. [0122] PEGylated Lipid [0123] In some aspects, an LNP can further comprise at least about 0.25%, or at least about 0.5%, or at least about 0.75%, or at least about 1.0%, or at least about 2.5%, or at least about 5%, or at least about 7.5%, or at least about 10% PEGylated lipid by moles. [0124] As used herein, the term “PEGylated lipid” is used to refer to any lipid that is modified (e.g. covalently linked to) at least one polyethylene glycol molecule. In some aspects, a PEGylated lipid can comprise 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000, hereafter referred to as “DMG-PEG2000” or “DMG-PEG”. [0125] In some aspects, the at least one PEGylated lipid is a mixture of two PEGylated lipids. [0126] Exemplary LNP Compositions [0127] The following are exemplary LNP compositions of the present disclosure comprising at least one compound of Formula (I), Formula (II’), and/or Formula (II), at least one structural lipid, at least one PEGylated lipid and at least one phospholipid. [0128] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% to about 50% of at least one compound of Formula (I) by moles, about 37.5% to about 56% of at least one structural lipid by moles, about 5% to about 12% of at least one phospholipid by moles, and about 1% to about 2.5% of at least one PEGylated lipid by moles. [0129] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% of at least one compound of Formula (I) by moles, about 56% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles. [0130] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 38.5% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles. [0131] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 37.5% at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 2.5% of at least one PEGylated lipid by moles. [0132] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 40% of at least one compound of Formula (I) by moles, about 52.5% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 2.5% of at least one PEGylated lipid by moles. [0133] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 45% of at least one compound of Formula (I) by moles, about 45.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 2% of at least one PEGylated lipid by moles. [0134] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 43.17% of at least one compound of Formula (I) by moles, about 43.17% of at least one structural lipid by moles, about 11.96% of at least one phospholipid by moles, and about 1.7% of at least one PEGylated lipid by moles. [0135] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 45% of at least one compound of Formula (I) by moles, about 43% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 2% of at least one PEGylated lipid by moles. [0136] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 45% of at least one compound of Formula (I) by moles, about 46% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles. [0137] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 39% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0138] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 41.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0139] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 40% of at least one compound of Formula (I) by moles, about 48.5% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles. [0140] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% to about 50% of at least one compound of Formula (II) by moles, about 37% to about 59% of at least one structural lipid by moles, about 5% to about 10% of at least one phospholipid by moles, and about 1% to about 3% of at least one PEGylated lipid by moles. [0141] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% of at least one compound of Formula (II) by moles, about 59% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0142] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II) by moles, about 41.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0143] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II) by moles, about 39% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0144] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 42.5% of at least one compound of Formula (II) by moles, about 51.5% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0145] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% to about 50% of at least one compound of Formula (II’) by moles, about 37% to about 59% of at least one structural lipid by moles, about 5% to about 10% of at least one phospholipid by moles, and about 1% to about 3% of at least one PEGylated lipid by moles. [0146] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% of at least one compound of Formula (II’) by moles, about 59% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0147] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II’) by moles, about 41.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0148] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II’) by moles, about 39% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0149] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 42.5% of at least one compound of Formula (II’) by moles, about 51.5% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles. [0150] In some aspects of the preceding LNPs, the compound of Formula (I), Formula (II’), or Formula (II) comprised in the LNP composition is one of COMPOUND NOS.1-14. [0151] In some aspects, the compound of Formula (I), Formula (II’), or Formula (II) is one of COMPOUND NOS.1-14. [0152] In some aspects of the preceding LNPs, the compound of Formula (I), Formula (II’), or Formula (II) comprised in the LNP composition is one of COMPOUND NOS.1-22. [0153] In some aspects, the compound of Formula (I), Formula (II’), or Formula (II) is one of COMPOUND NOS.1-22. [0154] In some aspects, the structural lipid can be cholesterol. [0155] In some aspects, the phospholipid is DOPE. [0156] In some aspects, the phospholipid is DSPC. [0157] In some aspects, the phospholipid is DOPC. [0158] In some aspects, the phospholipid is DPPC. [0159] In some aspects, the phospholipid can be a mixture of DSPC and DOPC. In some aspects, the mixture of DSPC and DOPC can comprise DSPC and DOPC at a 1:1 ratio (e.g. a LNP that comprises 10% phospholipid can comprise 5% DOPC and 5% DSPC). [0160] In some aspects of the preceding LNPs, the PEGylated lipid can be DMG-PEG2000. [0161] In some aspects, the structural lipid can be cholesterol, the phospholipid can be DOPE and the PEGylated lipid can be DMG-PEG2000. [0162] In some aspects, the structural lipid can be cholesterol, the phospholipid can be DOPC and the PEGylated lipid can be DMG-PEG2000. [0163] In some aspects, the structural lipid can be cholesterol, the phospholipid can be DSPC and the PEGylated lipid can be DMG-PEG2000. [0164] In some aspects, the structural lipid can be cholesterol, the phospholipid can be DPPC and the PEGylated lipid can be DMG-PEG2000. [0165] In some aspects, the structural lipid can be cholesterol, the phospholipid can be a mixture of DSPC and DOPC, and the PEGylated lipid can be DMG-PEG2000. In some aspects, the mixture of DSPC and DOPC can comprise DSPC and DOPC at a 1:1 ratio (e.g. a LNP that comprises 10% phospholipid can comprise 5% DOPC and 5% DSPC). [0166] Table 1A shows further exemplary LNP compositions of the present disclosure. Table 1A [0167] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the compound of Formula (I), Formula (II), or Formula (II’) is one of COMPOUND NOS.1-22. [0168] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the structural lipid can be cholesterol. [0169] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the phospholipid is DOPE. [0170] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the phospholipid is DSPC. [0171] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the phospholipid is DOPC. [0172] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the phospholipid is DPPC. [0173] In some aspects of the preceding LNPs, including the LNP compositions put forth in Table 1, the PEGylated lipid can be DMG-PEG2000. [0174] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the structural lipid can be cholesterol, the phospholipid can be DOPE and the PEGylated lipid can be DMG-PEG2000. [0175] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the structural lipid can be cholesterol, the phospholipid can be DOPC and the PEGylated lipid can be DMG-PEG2000. [0176] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the structural lipid can be cholesterol, the phospholipid can be DSPC and the PEGylated lipid can be DMG-PEG2000. [0177] In some aspects, including in the LNP compositions put forth in Tables 1A-1C, the structural lipid can be cholesterol, the phospholipid can be DPPC and the PEGylated lipid can be DMG-PEG2000. [0178] Targeting Ligand [0179] In some aspects, an LNP, including those put forth in Table 1A, can further comprise at least one targeting ligand. [0180] In some aspects, an LNP can further comprise at least about 0.05%, or at least about 0.1%, or at least about 0.15%, or at least about 0.2%, or at least about 0.25%, or at least about 0.3%, or at least about 0.35%, or at least about 0.4%, or at least about 0.45%, or at least about 0.5%, or at least about 0.55%, or at least about 0.6%, or at least about 0.65%, or at least about 0.7%, or at least about 0.75%, or at least about 0.8%, or at least about 0.85%, or at least about 0.9%, or at least about 0.95%, or at least about 1.0%, or at least about 1.1%, or at least about 1.2%, or at least about 1.3%, or at least about 1.4%, or at least about 1.5%, or at least about 1.6%, or at least about 1.7%, or at least about 1.8%, or at least about 1.9%, or at least about 2.0% targeting ligand by moles. [0181] A targeting ligand may be any ligand that provides an enhanced affinity for a selected target, e.g., molecule, cell or cell type, e.g., a cellular or organ compartment, tissue, organ or region of the body, as, e.g., compared to a species absent such a ligand. [0182] Without wishing to be bound by any theory, a composition comprising a targeting lipid is well-tolerated and provides an adequate therapeutic index, such that patient treatment with an effective dose of the composition is associated with an improved toxicity and/or risk profile to the patient, compared to patient treatment with an effective dose of a composition that does not comprise a targeting ligand. [0183] In some aspects, a targeting ligand provides an enhanced affinity for the liver or liver cells, such as hepatocytes. A non-limiting example of a targeting ligand with enhanced affinity for the liver or liver cells is GalNac (n-acetyl-galactosamine). Thus, in some embodiments, the disclosure provides compositions comprising a targeting ligand comprising GalNac. [0184] In some aspects, a targeting ligand comprising GalNac can be a pegylated GalNac molecule. In some aspects, a pegylated GalNac molecule can be Tri-GalNac-PEG2000-DSPE (referred to herein as “GalNac-PEG”), and which structure is shown below: . [0185] Thus, in some aspects, the present disclosure provides LNPS comprising GalNac- PEG.In some aspects, a targeting ligand can also include targeting groups, for example a group of tissue targeting agents. A non-limiting example of a targeting group can be a multivalent GalNac molecule. Thus, in some embodiments, the disclosure provides LNP compositions comprising a targeting ligand comprising multivalent GalNac. A non-limiting example of a multivalent GalNac molecule is GalNac-PEG. [0186] Table 1B shows exemplary LNP compositions of the present disclosure comprising at least one compound of Formula (I), Formula (II), or Formula (II’), at least one structural lipid, at least one PEGylated lipid and at least one phospholipid, and at least one targeting ligand comprising GalNac. Table 1B [0187] In some aspects, including in the LNPS of Table 1B, the targeting ligand comprising GalNac is GalNac-PEG. [0188] Nucleic Acid Molecules [0189] In some aspects, a lipid nanoparticle of the present disclosure, , including those put forth in Tables 1A and 1B, can further comprise at least one nucleic acid. In some aspects, a lipid nanoparticle can comprise a plurality of nucleic acid molecules. In some aspects, the at least one nucleic acid or the plurality of nucleic acid molecules can be formulated in a lipid nanoparticle. [0190] Accordingly, a lipid nanoparticle can comprise at least one nucleic acid, at least one compound of the present disclosure, at least one structural lipid, at least one phospholipid, and at least one PEGylated lipid. In some aspects, the lipid nanoparticle can further comprise at least one targeting ligand. [0191] In some aspects, the at least one nucleic acid molecule is a DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. [0192] In some aspects of the preceding LNPs, the at least one nucleic acid molecule is an RNA molecule. In some aspects, the RNA molecule is an mRNA molecule. In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, all of the cytidine residues in an mRNA molecule can be 5-methylcytidine. [0193] In some aspects, the at least one RNA molecule is a guide RNA (gRNA) molecule. [0194] In some aspects, an at least one nucleic acid can comprise both mRNA molecules and guide RNA (gRNA) molecules. That is, the LNPs of the present disclosure can comprise both mRNA molecules and gRNA molecules. In some aspects wherein the LNPs comprise both mRNA molecules and gRNA molecules, the mRNA molecules comprise at least one nucleic acid sequence that encodes a fusion protein, wherein the fusion protein comprises: (i) an inactivated Cas9 (dCas9) protein or an inactivated nuclease domain thereof; and (ii) a Clo051 protein or a nuclease domain thereof, and wherein the gRNA molecules encode guide RNA sequence targeting one or more specific genomic loci. In some aspects, the fusion protein can be a Cas-CLOVER protein. In some aspects, the gRNA molecules can target the psk9 gene. [0195] In some aspects wherein the LNPs comprise both mRNA molecules and gRNA molecules, the ratio of mRNA:gRNA can be about 1:2, or about 1:3, or about1:4, or about 1:5, or about 1:6, or about 1:7, or about 1:8, or about 1:9, or about 1:10 or about 1:1, or about 2:1, or about 3:1, or about 4:1, or about 5:1, or about 6:1, or about 7:1, or about 8:1, or about 9:1 or about 10:1. [0196] In some aspects, an at least one nucleic acid can comprise at least one RNA molecule and at least one DNA molecule. That is, the LNPs of the present disclosure can comprise both RNA molecules and DNA molecules. [0197] In some aspects, the LNPs of the present disclosure can comprise both RNA molecules and DNA molecules, wherein the RNA molecules comprise at least one nucleic acid sequence that encodes a transposase and wherein the DNA molecules comprise at least one nucleic acid sequence that comprises a transposon. In some aspects, the transposase can be any of the transposases described herein. In some aspects, the transposon can be a transposon comprising at least one nucleic acid sequence encoding a FVIII polypeptide. [0198] In some aspects wherein the LNPs of the present disclosure comprise both RNA (e.g. mRNA) and DNA, the ratio of RNA to DNA (RNA:DNA) in the LNPs can be about 1:2, or about 1:3, or about 1:4, or about 1:1, or about 2:1, or about 3:1, or about 4:1, or about 5:1, or about 6:1, or about 7:1, or about 8:1, or about 9:1 or about 10:1. [0199] In some aspects, a lipid nanoparticle can comprise lipid and nucleic acid at a specified ratio (weight/weight). [0200] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise lipid and nucleic acid at a ratio of about 5:1 to about 15:1, or about 10:1 to about 20:1, or about 15:1 to about 25:1, or about 20:1 to about 30:1, or about 25:1 to about 35:1 or about 30:1 to about 40:1, or about 35:1 to about 45:1, or about 40:1 to about 50:1, or about 45:1 to about 55:1, or about 50:1 to about 60:1, or about 55:1 to about 65:1, or about 60:1 to about 70:1, or about 65:1 to about 75:1, or about 70:1 to about 80:1, or about 75:1 to about 85:1, or about 80:1 to about 90:1, or about 85:1 to about 95:1, or about 90:1 to about 100:1, or about 95:1 to about 105:1, or about 100:1 to about 110:1, or about 105:1 to about 115:1, or about 110:1 to about 120:1, or about 115:1 to about 125:1, or about 120:1 to about 130:1, or about 125:1 to about 135:1, or about 130:1 to about 140:1, or about 135:1 to about 145:1, or about 140:1 to about 150:1, lipid:nucleic acid, weight/weight. [0201] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise lipid and nucleic acid at a ratio of about 5:1, or about 10:1, or about 15:1, or about 20:1, or about 25:1, or about 30:1, or about 35:1, or about 40:1, or about 45:1, or about 50:1, or about 55:1, or about 60:1, or about 65:1, or about 70:1, or about 75:1, or about 80:1, or about 85:1, or about 90:1, or about 95:1, or about 100:1, or about 105:1, or about 110:1, or about 115:1, or about 120:1, or about 125:1, or about 130:1, or about 135:1, or about 140:1, or about 145:1, or about 150:1, lipid:nucleic acid, weight/weight. [0202] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise lipid and nucleic acid at a ratio of about 10:1, or about 25:1, or about 40:1, lipid:nucleic acid, weight/weight. [0203] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise lipid and nucleic acid at a ratio of about 20:1, or about 40:1, or about 60:1, or about 80:1, or about 120:1 lipid:nucleic acid, weight/weight. [0204] Further characteristics of the nucleic acid molecules of the present disclosure are provided herein. [0205] Polyphenol Additives [0206] In some aspects, a lipid nanoparticle of the present disclosure, , including those put forth in Tables 1A and 1B, can further comprise at least one polyphenol (also referred to herein as a “polyphenol additive”). [0207] As used herein, the term “polyphenol” is used to refer to any compound that has at least two phenol subunits, wherein a phenol is an aromatic ring, as defined herein, that has at least one hydroxyl substituent. Polyphenols include compounds that have at least two phenol subunits, for example flavonoids, catechins, anthocyanins, stilbenes and ellagic acid. Polyphenols also include compounds that have at least three phenol subunits, for example proanthocyanins, tannins and punicalagin. [0208] Accordingly, a lipid nanoparticle can comprise at least one compound of the present disclosure, at least one structural lipid, at least one phospholipid, at least one PEGylated lipid, and at least one polyphenol. In some aspects, the lipid nanoparticle can further comprise, at least one nucleic acid, at least one targeting ligand, or any combination thereof. [0209] In some aspects, the at least one polyphenol is selected from: malvidin 3-o-(6"-p- coumaroyl- glucoside), delphinidin 3-o-(6"-acetyl-galactoside), cyanidin 3-o-(6"-acetyl- galactoside), cyanidin 3-o-galactoside, cyanidin 3-o-glucoside, cyanidin 3-o-rutinoside, cyanidin 3-o- sophoroside, pelargonidin 3-o-glucoside, cyanidin 3-o-(6"-malonyl-glucoside), peonidin, peonidin 3-o-glucoside, peonidin 3-o-rutinoside, pelargonidin 3-o-rutinoside, pelargonidin, cyanidin, malvidin 3,5-o-diglucoside, cyanidin 3-o-glucosyl-rutinoside, pelargonidin 3-o- sophoroside, pelargonidin 3-o-glucosyl-rutinoside, cyanidin 3-o-(6"- succinyl-glucoside), pelargonidin 3-o-(6"-succinyl-glucoside), delphinidin 3-o-galactoside, delphinidin 3-o-glucoside, delphinidin 3-o-arabinoside, petunidin 3-o-galactoside, cyanidin 3- o-arabinoside, petunidin 3-o- glucoside, peonidin 3-o-galactoside, petunidin 3-o-arabinoside, malvidin 3-o-glucoside, malvidin 3-o-arabinoside, delphinidin 3-o-(6"-acetyl-glucoside), petunidin 3-o-(6"-acetyl-galactoside), peonidin 3-o-(6"-acetyl-galactoside), cyanidin 3-o-(6"- acetyl-glucoside), malvidin 3-o-(6"-acetyl- galactoside), petunidin 3-o-(6"-acetyl-glucoside), malvidin 3-o-(6"-acetyl-glucoside), peonidin 3- o-(6"-acetyl-glucoside), pelargonidin 3-o- arabinoside, delphinidin 3-o-rutinoside, cyanidin 3-o- sambubioside, pelargonidin 3-o-(6"- malonyl-glucoside), peonidin 3-o-(6"-p-coumaroyl- glucoside), cyanidin 3-o-xyloside, malvidin 3-o-galactoside, peonidin 3-o-arabinoside, petunidin 3-o-rutinoside, delphinidin 3- o-xyloside, petunidin 3-o-(6"-p-coumaroyl-glucoside), pelargonidin 3-o-galactoside, pelargonidin 3-o-sambubioside, delphinidin 3-o-sambubioside, cyanidin 3-o- xylosyl- rutinoside, vitisin a, delphinidin 3-o-(6"-p-coumaroyl-glucoside), pigment a, cyanidin 3- o- (6"-p-coumaroyl-glucoside), cyanidin 3-o-sambubioside 5-o-glucoside, cyanidin 3-o-(6"- caffeoyl-glucoside), cyanidin 3,5-o-diglucoside, pinotin a, delphinidin 3,5-o-diglucoside, pelargonidin 3,5-o-diglucoside, malvidin 3-o-(6"-caffeoyl-glucoside), cyanidin 3-o-(6"- dioxalyl- glucoside), delphinidin 3-o-glucosyl-glucoside, cyanidin 3-o-(6"-malonyl-3"- glucosyl- glucoside), delphinidin 3-o-feruloyl-glucoside, petunidin 3,5-o-diglucoside, petunidin 3-o- rhamnoside, cyanidin 3-o-diglucoside-5-o-glucoside, peonidin 3-o- diglucoside-5-o-glucoside, peonidin 3-o-(2-o-(6-o-(e)-caffeoyl-d-glucosyl)-d-glucoside)-5-o- d-glucoside, peonidin 3-o- sophoroside, peonidin 3-o-sambubioside, peonidin 3-o- sambubioside-5-o-glucoside, peonidin 3- o-xyloside, 4'-o-methylcyanidin 3-o-d-glucoside, cyanidin 3-o-(3",6"-o-dimalonyl-glucoside), 4- o-methyldelphinidin 3-o-d-glucoside, isopeonidin 3-o-arabinoside, isopeonidin 3-o-galactoside, isopeonidin 3-o-glucoside, isopeonidin 3-o-rutinoside, isopeonidin 3-o-sambubioside, isopeonidin 3-o-xyloside, cyanidin 3-o-(2-o-(6-o-(e)-caffeoyl-d glucoside)-d-glucoside)-5-o-d- glucoside, 4'-o-methyldelphinidin 3-o-rutinoside, butein, xanthohumol, phloretin, phloridzin, phloretin 2'-o-xylosyl-glucoside, 3-hydroxyphloretin 2'-o-xylosyl-glucoside, 3-hydroxyphloretin 2'-o-glucoside, phloretin 2'-o- glucuronide, dihydroquercetin 3-o-rhamnoside, dihydroquercetin, dihydromyricetin 3-o- rhamnoside, (+)-catechin, (-)-epi catechin, (+)-gallocatechin, (-)- epigallocatechin, (-)- epicatechin 3-o-gallate, (-)-epigallocatechin 3-o-gallate, theaflavin, theaflavin 3-o-gallate, theaflavin 3'-o-gallate, theaflavin 3,3'-o-digallate, (+)-gallocatechin 3-o- gallate, (+)-catechin 3-o-gallate, procyanidin dimer bl, procyanidin dimer b2, procyanidin dimer b3, procyanidin dimer b4, procyanidin dimer b5, procyanidin dimer b7, prodelphinidin dimer b3, procyanidin trimer cl, procyanidin trimer eec, procyanidin trimer t2, procyanidin trimer c2, prodelphinidin trimer gc-gc-c, prodelphinidin trimer gc-c-c, prodelphinidin trimer c-gc-c, (-)- epicatechin- (2a-7)(4a-8)-epicatechin 3-o-galactoside, cinnamtannin a2, (+)-catechin 3-o-glucose, 3'-o- methylepicatechin, 4'-o-methyl-(-)-epicatechin 3'-o-glucuronide, epicatechin 3'-o- glucuronide, 3'-o-methylcatechin, 4',4"-o-dimethylepigallocatechin 3-o-gallate, 4'-o- methylepigallocatechin, 4"-o-methylepigallocatechin 3-o-gallate, 4'-o-methylepicatechin, epigallocatechin 3-o-gallate-7-o-glucoside-4"-o-glucuronide, (-)-epigallocatechin 3-o- glucuronide, 3'-o-methyl-(-)-epicatechin 7-o-glucuronide, epicatechin 7-o-glucuronide, (-)- epigallocatechin 3'-o-glucuronide, (-)-epigallocatechin 7-o-glucuronide, 4'-o-methyl-(-)- epigallocatechin 3'-o-glucuronide, 4'-o-methyl-(-)-epigallocatechin 7-o-glucuronide, naringenin, eriodictyol, hesperetin, eriocitrin, hesperidin, naringin, narirutin, neoeriocitrin, neohesperidin, poncirin, didymin, narirutin 4'-o-glucoside, naringin 4'-o-glucoside, naringin 6'-malonate, isosakuranetin, naringenin 7-o-glucoside, pinocembrin, 8-prenylnaringenin, 6- prenylnaringenin, 6-geranylnaringenin, isoxanthohumol, eriodictyol 7-o-glucoside, sakuranetin, hesperetin 3'-o- glucuronide, hesperetin 7-o-glucuronide, hesperetin 3'-sulfate, homoeriodictyol, naringenin 4'-o- glucuronide, naringenin 5-o-glucuronide, naringenin 7-o- glucuronide, hesperetin 3',7-o- diglucuronide, hesperetin 5,7-o-diglucuronide, apigenin, luteolin, diosmin, isorhoifolin, neodiosmin, rhoifolin, sinensetin, nobiletin, tangeretin, luteolin 7-o-diglucuronide, chrysin, luteolin 7-o-rutinoside, tetramethylscutellarein, luteolin 7-o-glucoside, apigenin 7-o-glucoside, apigenin 6,8-di-c-glucoside, apigenin 6,8-c- arabinoside-c-glucoside, apigenin 6,8-c-galactoside- c-arabinoside, luteolin 7-o-glucuronide, apigenin 7-o-glucuronide, luteolin 7-o-malonyl- glucoside, luteolin 6-c-glucoside, luteolin 7- o-(2-apiosyl-glucoside), luteolin 7-o-(2-apiosyl-6- malonyl)-glucoside, apigenin 7-o-apiosyl- glucoside, 7,3',4'-trihydroxyflavone, 7,4'- dihydroxyflavone, geraldone, baicalein, apigenin 6- c-glucoside, hispidulin, cirsimaritin, 5,6- dihydroxy-7,8,3',4'-tetramethoxyflavone, pebrellin, gardenin b, nepetin, jaceosidin, cirsilineol, eupatorin, 6-hydroxyluteolin, 6-hydroxyluteolin 7- o-rhamnoside, scutellarein, apigenin 7-o-(6"- malonyl-apiosyl-glucoside), chrysoeriol 7-o- apiosyl-glucoside, chrysoeriol 7-o-(6"-malonyl- apiosyl-glucoside), chrysoeriol 7-o- glucoside, chrysoeriol 7-o-(6"-malonyl-glucoside), apigenin 7-o-diglucuronide, rhoifolin 4'-o- glucoside, kaempferol, quercetin, quercetin 3-o-galactoside, quercetin 3-o-glucoside, quercetin 3-o-xyloside, quercetin 3-o-rhamnoside, quercetin 3-o- rutinoside, quercetin 3-o- sophoroside, quercetin 3-o-arabinoside, quercetin 3-o-xylosyl- glucuronide, isorhamnetin 3- o-glucoside 7-o-rhamnoside, isorhamnetin 3-o-rutinoside, kaempferol 3-o-glucuronide, isorhamnetin 7-o-rhamnoside, quercetin 3,4'-o-diglucoside, myricetin 3-o-rutinoside, myricetin, morin, kaempferide, myricetin 3-o-galactoside, myricetin 3- o-glucoside, quercetin 3-o-glucosyl-xyloside, quercetin 3-o-acetyl-rhamnoside, kaempferol 3-o- galactoside, galangin, isorhamnetin, kaempferol 3-o-glucoside, kaempferol 3-o-rutinoside, kaempferol 3- o-glucosyl-rhamnosyl-galactoside, kaempferol 3-o-glucosyl-rhamnosyl-glucoside, quercetin 3-o-glucosyl-rhamnosyl-galactoside, quercetin 3-o-glucosyl-rhamnosyl-glucoside, rhamnetin, isorhamnetin 3-o-glucoside, myricetin 3-o-rhamnoside, quercetin 3-o-rhamnosyl- galactoside, quercetin 3-o-glucuronide, isorhamnetin 3-o-glucuronide, myricetin 3-o-arabinoside, quercetin 7,4'-o-diglucoside, quercetin 4'-o-glucoside, isorhamnetin 4'-o-glucoside, 3,7- dimethylquercetin, kaempferol 3-o-sophoroside, kaempferol 3,7-o-diglucoside, kaempferol 3- o- sophoroside 7-o-glucoside, quercetin 3-o-(6"-malonyl-glucoside), kaempferol 3-o-(6"- malonyl- glucoside), kaempferol 3-o-rhamnoside, quercetin 3-o-(6"-malonyl-glucoside) 7-o- glucoside, patuletin 3-o-glucosyl-(l->6)-[apiosyl(l->2)]-glucoside, spinacetin 3-o-glucosyl-(l- >6)- [apiosyl(l->2)]-glucoside, patuletin 3-o-(2"-feruloylglucosyl)(l->6)-[apiosyl(l->2)]- glucoside, spinacetin 3-o-(2"-p-coumaroylglucosyl)(l->6)-[apiosyl(l->2)]-glucoside, spinacetin 3-o-(2"- feruloylglucosyl)( 1 ->6)-[apiosyl( 1 ->2)]-glucoside, spinacetin 3 -o- glucosyl-( 1 ->6)-glucoside, jaceidin 4’-o-glucuronide, 5,3',4'-trihydroxy-3-methoxy-6:7- methylenedioxyflavone 4'-o- glucuronide, 5,4'-dihydroxy-3,3'-dimethoxy-6:7- methylenedioxyflavone 4'-o-glucuronide, kaempferol 3-o-xylosyl-glucoside, kaempferol 3-o- acetyl-glucoside, quercetin 3-o-xylosyl- rutinoside, kaempferol 3-o-xylosyl-rutinoside, kaempferol 7-o-glucoside, kaempferol 3-o- galactoside 7-o-rhamnoside, kaempferol 3-o-(6"- acetyl-galactoside) 7-o-rhamnoside, quercetin 3-o-galactoside 7-o-rhamnoside, quercetin 3-o- (6"-acetyl-galactoside) 7-o-rhamnoside, kaempferol 3-o-(2"-rhamnosyl-galactoside) 7-o- rhamnoside, kaempferol 3-o-(2"-rhamnosyl-6"- acetyl-galactoside) 7-o-rhamnoside, 6,8- dihydroxykaempferol, isorhamnetin 3-o-galactoside, quercetin 3 -o-rhamnosyl-rhamnosyl - glucoside, kaempferol 3-o-rhamnosyl-rhamnosyl-glucoside, methylgalangin, kaempferol 3,7,4'-o-triglucoside, 3-methoxynobiletin, 3-methoxysinensetin, quercetin 3'-o-glucuronide, quercetin 3'-sulfate, quercetin 4'-o-glucuronide, isorhamnetin 4'-o- glucuronide, daidzein, formononetin, genistein, biochanin a, glycitein, glycitin, 6"-o- acetyldaidzin, 6"-o- malonylgenistin, daidzin, genistin, 6"-o-acetylgenistin, 6"-o-acetylglycitin, 6"-o- malonyldaidzin, 6"-o-malonylglycitin, 2',7-dihydroxy-4',5'-dimethoxyisoflavone, 2- dehydro- o-desmethylangolensin, 2'-hydroxyformononetin, 3',4',7-trihydroxyisoflavan, 3', 4', 7- trihydroxyisoflavanone, 3'-hydroxydaidzein, 3'-hydroxy-o-desmethylangolensin, 4', 6, 7- trihydroxyisoflavanone, 4',7-dihydroxy-3'-methoxyisoflavan, 4',7-dihydroxy-6- m ethoxy isoflavan, 4'-o-methylequol, 5,6,7,3',4'-pentahydroxyisoflavone, 5, 6,7,4'- tetrahydroxyisoflavone, 5,7,8,3',4'-pentahydroxyisoflavone, 5,7,8,4'-tetrahydroxyisoflavone, 5'- hydroxy-o-desmethylangolensin, 5'-methoxy-o-desmethylangolensin, 6, 7, 3', 4'- tetrahydroxyisoflavone, 6,7,4'-trihydroxyisoflavone, 6'-hydroxyangolensin, 6'-hydroxy-o- desmethylangolensin, 7,8,3',4'-tetrahydroxyisoflavone, 7,8,4'-trihydroxyisoflavone, angolensin, calycosin, daidzein 4'-o-glucuronide, daidzein 7-o-glucuronide, dihydrobiochanin a, dihydrodaidzein, dihydrodaidzein 7-o-glucuronide, dihydroformononetin, dihydrogeni stein, dihydroglycitein, equol, formononetin 7-o-glucuronide, genistein 4',7-o-diglucuronide, genistein 4'-o-glucuronide, genistein 5-o-glucuronide, genistein 7-o-glucuronide, glycitein 4'- o- glucuronide, glycitein 7-o-glucuronide, koparin, o-desmethylangolensin, orobol, prunetin, pseudobaptigenin, puerarin, daidzin 4'-o-glucuronide, irisolidone 7-o-glucuronide, tectorigenin 7-sulfate, tectorigenin 4'-sulfate, irisolidone, tectorigenin, tectoridin, 5,7- dihydroxy-8,4'- dimethoxyisoflavone, isotectorigenin, equol 7-o-glucuronide, equol 4'-o- glucuronide, 3', 4', 5,7- tetrahydroxyisoflavanone, 3'-o-methylequol, 6-o-methylequol, 3'- hydroxygenistein, 6- hydroxydihydrodaidzein, 3 '-hydroxy equol, cis-4-hydroxyequol, 4'- methoxy-2',3,7- trihydroxyisoflavanone, irilone, vestitone, sativanone, butin, 3'- hydroxymelanettin, melanettin, stevenin, violanone, isoliquiritigenin, dalbergin, 3'-o- methylviolanone, 8- hydroxydihydrodaidzein, secoisolariciresinol, matairesinol, lariciresinol, pinoresinol, syringaresinol, isolariciresinol, arctigenin, trachelogenin, medioresinol, 1- acetoxypinoresinol, sesamin, sesamolin, sesamolinol, sesaminol, sesamol, 7- hydroxymatairesinol, isohydroxymatairesinol, secoisolariciresinol-sesquilignan, cyclolariciresinol, 7-oxomatairesinol, todolactol a, conidendrin, 7- hydroxysecoisolariciresinol, nortrachelogenin, lariciresinol- sesquilignan, anhydro- secoisolariciresinol, dimethylmatairesinol, episesamin, episesaminol, enterodiol, enterolactone, sesaminol 2-o-triglucoside, schisandrin, gomisin d, schisandrol b, tigloylgomicin h, schisanhenol, schisantherin a, gomisin m2, deoxyschisandrin, schisandrin b, schisandrin c, 2-hydroxyenterodiol, 4-hydroxyenterodiol, 6-hydroxyenterodiol, 2- hydroxyenterolactone, 4-hydroxy enterolactone, 6-hydroxyenterolactone, 2'- hydroxyenterolactone, 4'-hydroxyenterolactone, 6'-hydroxyenterolactone, 5- hydroxyenterolactone, 7-hydroxyenterolactone, 4-ethylbenzoic acid, glycine, 1,3,5- trimethoxybenzene, vanilloylglycine, 4-vinylguaiacol, 4-ethylguaiacol, 4-vinylsyringol, 5- heneicosenylresorcinol, 5 -heneicosylresorcinol, 5-heptadecylresorcinol, 5- nonadecenylresorcinol, 5-nonadecylresorcinol, 5-pentacosenylresorcinol, 5- pentacosylresorcinol, 5-pentadecylresorcinol, 5-tricosenylresorcinol, 5-tricosylresorcinol, 3- methylcatechol, 4- methylcatechol, 4-ethylcatechol, 4-vinylphenol, 4-ethylphenol, curcumin, demethoxycurcumin, bisdem ethoxy curcumin, bergapten, psoralen, xanthotoxin, isopimpinellin, syringaldehyde, protocatechuic aldehyde, vanillin, 4-hydroxybenzaldehyde, gallic aldehyde, p-anisaldehyde, vanillin 4-sulfate, 3 -meth oxy acetophenone, 2,3 - dihydroxy- 1-guaiacylpropanone, paeonol, 2,4- dihydroxyacetophenone 5-sulfate, 2-hydroxy- 4-methoxyacetophenone 5-sulfate, resacetophenone, norathyriol, ferulaldehyde, sinapaldehyde, coumarin, mellein, scopoletin, esculetin, esculin, umbelliferone, 4- hydroxycoumarin, urolithin a 3,8-o-diglucuronide, urolithin a, urolithin b, urolithin b 3-o- glucuronide, urolithin c, 2-methoxy-5-prop-l-enylphenol, anethole, eugenol, acetyl eugenol, [6]-gingerol, estragole, guaiacol, juglone, 1,4-naphtoquinone, camosic acid, rosmanol, carnosol, epirosmanol, rosmadial, thymol, carvacrol, tyrosol, hydroxytyrosol, 3,4-dhpea-ac, p-hpea-ac, oleuropein, demethyloleuropein, 3,4-dhpea-ea, ligstroside, 3,4-dhpea- eda, hydroxytyrosol 4-o-glucoside, oleoside dimethylester, oleoside 11 -methylester, p-hpea-eda, p-hpea-ea, ol europein-aglycone, ligstroside-aglycone, tyrosol 4-sulfate, coumestrol, catechol, pyrogallol, phlorin, phenol, arbutin, 3,4-dihydroxyphenylglycol, lithospermic acid, salvianolic acid b, salvianolic acid c, salvianolic acid d, salvianolic acid g, isopropyl 3-(3,4- dihydroxyphenyl)-2-hydroxypropanoate, ellagic acid glucoside, protocatechuic acid, gallic acid, vanillic acid, gentisic acid, ellagic acid, 4-hydroxybenzoic acid, syringic acid, 5-o- galloylquinic acid, ellagic acid arabinoside, ellagic acid acetyl-xyloside, ellagic acid acetyl- arabinoside, benzoic acid, 2-hydroxybenzoic acid, 3 -hydroxybenzoic acid, 2,3 - dihydroxybenzoic acid, 2,4- dihydroxybenzoic acid, 4-hydroxybenzoic acid 4-o-glucoside, protocatechuic acid 4-o-glucoside, gallic acid 4-o-glucoside, 3,5-dihydroxybenzoic acid, 2,6- dihydroxybenzoic acid, gallic acid 3-o- gallate, gallic acid ethyl ester, valoneic acid dilactone, galloyl glucose, lambertianin c, sanguiin h-6, punicalagin, gallagic acid, 3-o-methylgallic acid, 4-o-m ethylgallic acid, 3,4-o-dimethylgallic acid, punicalin, 4-hydroxyhippuric acid, 3 - hydroxy hippuric acid, 2-hydroxyhippuric acid, hippuric acid, paeoniflorin, vanillic acid 4- sulfate, p-coumaric acid, 5-p-coumaroylquinic acid, 4- p-coumaroylquinic acid, caffeic acid, feruloyl glucose, ferulic acid, caffeoyl tartaric acid, rosmarinic acid, o-coumaric acid, m- coumaric acid, sinapic acid, p-coumaroyl glucose, p- coumaroylquinic acid, 3-caffeoylquinic acid, verbascoside, 4-caffeoylquinic acid, p-coumaroyl tartaric acid, 2,5-di-s-glutathionyl caftaric acid, feruloyl tartaric acid, caffeic acid ethyl ester, cinnamoyl glucose, 5- caffeoylquinic acid, 3-p-coumaroylquinic acid, 2-s-glutathionyl caftaric acid, 5-feruloylquinic acid, 4-feruloylquinic acid, 3-feruloylquinic acid, 5-sinapoylquinic acid, 4- sinapoylquinic acid, 3-sinapoylquinic acid, 3,5-dicaffeoylquinic acid, isoferulic acid, caffeoyl glucose, p- coumaric acid 4-o-glucoside, caffeic acid 4-o-glucoside, ferulic acid 4-o-glucoside, p- coumaroyl tartaric acid glucosidic ester, p-coumaric acid ethyl ester, hydroxycaffeic acid, chicoric acid, 5-5'-dehydrodiferulic acid, 5-8'-dehydrodiferulic acid, 1,2- disinapoylgentiobiose, l-sinapoyl-2-feruloylgentiobiose, 1,2-diferuloylgentiobiose, l,2,2'- trisinapoylgentiobiose, 1,2'- disinapoyl-2-feruloylgentiobiose, l-sinapoyl-2,2'- diferuloylgentiobiose, 1,2,2'- triferuloylgentiobiose, 8-o-4'-dehydrodiferulic acid, 5-8'- benzofuran dehydrodiferulic acid, 3,4- dicaffeoylquinic acid, 3,4-diferuloylquinic acid, 3,5- diferuloylquinic acid, 1,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, avenanthramide 2p, avenanthramide 2c, avenanthramide 2f, p- coumaroyl malic acid, p-coumaroyl glycolic acid, cinnamic acid, caffeoyl aspartic acid, p- coumaroyl tyrosine, sinapine, avenanthramide k, 24-methylcholestanol ferulate, 24- methylcholesterol ferulate, 24-methyllathosterol ferulate, stigmastanol ferulate, sitosterol ferulate, schottenol ferulate, 24- methylenecholestanol ferulate, 3-o-methylrosmarinic acid, feruloylglycine, isoferulic acid 3- o-glucuronide, isoferulic acid 3-sulfate, ferulic acid 4-sulfate, ferulic acid 4-o-glucuronide, caffeic acid 4-sulfate, caffeic acid 3-sulfate, feruloyl cl- glucuronide, isoferuloyl cl - glucuronide, caffeic acid 3-o-glucuronide, caffeic acid 4-o- glucuronide, caffeoyl cl - glucuronide, 1,5-diferuloylquinic acid, l-caffeoyl-5-feruloylquinic acid, l-feruloyl-5- caffeoylquinic acid, 3,4-dihydroxyphenylacetic acid, 4-hydroxyphenylacetic acid, homovanillic acid, homoveratric acid, methoxyphenylacetic acid, 3 -hydroxyphenylacetic acid, 2- hydroxyphenylacetic acid, phenacetylglycine, phenylacetic acid, 4-hydroxymandelic acid, 2- hydroxy-2-phenylacetic acid, homovanillic acid 4-sulfate, dihydro-p-coumaric acid, di hydrocaffeic acid, 3-hydroxy-3-(3-hydroxyphenyl)propionic acid, 3-(3,4- dihydroxyphenyl)-2- methoxypropionic acid, 3 -hydroxyphenylpropionic acid, dihydroferulic acid 4-sulfate, dihydrocaffeic acid 3-o-glucuronide, dihydrocaffeic acid 3 -sulfate, dihydroferulic acid, dihydroferulic acid 4-o-glucuronide, dihydrosinapic acid, dihydroferuloylglycine, danshensu, 3- methoxy-4-hydroxyphenyllactic acid, 3,4- dihydroxyphenyllactic acid methyl ester, hydroxydanshensu, 3 -phenylpropionic acid, 3 - hydroxy-4-m ethoxyphenyllactic acid, 4- hydroxyphenyl-2-propionic acid, 5-(3'-methoxy-4'- hydroxyphenyl)-y-valerolactone, 4-hydroxy- (3',4'-dihydroxyphenyl)valeric acid, 5-(3',4'- dihydroxyphenyl)-valeric acid, 5-(3',4',- dihydroxyphenyl)-y-valerolactone, 5-(3', 4', 5'- trihydroxyphenyl)-y -valerolactone, 5-(3',5'- dihydroxyphenyl)-y-valerolactone, 3 - hydroxyphenylvaleric acid, 5-(3',5'-dihydroxyphenyl)-y- valerolactone 3-o-glucuronide, trans-resveratrol, piceatannol, e-viniferin, pterostilbene, d- viniferin, pallidol, piceatannol 3- o-glucoside, pinosylvin, resveratrol 5-o-glucoside, resveratrol, resveratrol 3-o-glucoside, 3,4,5,4'-tetramethoxystilbene, 3'-hydroxy-3, 4,5,4'- tetramethoxystilbene, 4'-hydroxy-3,4,5- trimethoxystilbene, 4-hydroxy-3,5,4'-trimethoxystilbene, cis-resveratrol 3-o-glucuronide, cis- resveratrol 3-sulfate, cis-resveratrol 4'-o-glucuronide, cisresveratrol 4'-sulfate, resveratrol 3- sulfate, trans-resveratrol 3,5-disulfate, trans-resveratrol 3,4'- di sulfate, trans-resveratrol 3-o- glucuronide, trans-resveratrol 3-sulfate, trans-resveratrol 4'-o- glucuronide, trans-resveratrol 4'-sulfate, dihydroresveratrol, tannic acid, or any combination thereof. [0210] In some aspects, the at least one polyphenol is selected from: tannic acid, proanthocyanin, punicalagin, ellagic acid, theaflavin 3,3’-digallate, pentagalloylglucose, catechin gallate, 1,3,6-tri-O-galloyl-beta-D-glucose, tellimagrandin II, 1,2,3,6- tetragalloylglucose or geraniin. [0211] In some aspects, the at least one polyphenol is tannic acid. [0212] In some aspects, a lipid nanoparticle can comprise a polyphenol and nucleic acid at a specified ratio (weight/weight). [0213] In some aspects, a lipid nanoparticle comprising a polyphenol and at least one nucleic acid can comprise a polyphenol and nucleic acid at a ratio of about 0.1:1, or about 0.15:1, or about 0.2:1, or about 0.25:1, or about 0.3:1, or about 0.35:1, or about 0.4:1, or about 0.45:1, or about 0.5:1, or about 1:1, or about 1.5:1, or about 2:1, or about 2.5:1, or about 3:1, or about 3.5:1, or about 4:1, or about 4.5:1, or about 5:1, or about 5.5:1, or about 6:1, or about 6.5:1, or about 7:1, or about 7.5:1, or about 8:1, or about 8.5:1, or about 9:1, or about 9.5:1, or about 10:1, or about 10.5:1, or about 11:1, or about 11.5:1, or about 12:1, or about 12.5:1, or about 13:1, or about 13.5:1, or about 14:1, or about 14.5:1, or about 15:1, or about 15.5:1, or about 16:1, or about 16.5:1, or about 17:1, or about 17.5:1, or about 18:1, or about 18.5:1, or about 19:1, or about 19.5:1, or about 20:1 polyphenol:nucleic acid. [0214] In some aspects, a lipid nanoparticle comprising tannic acid and at least one nucleic acid can comprise tannic acid and nucleic acid at a ratio of about 0.15:1, or about 0.2:1, or about 5:1, or about 7:1, or about 7.5:1, or about 10:1, or about 12.5:1, or about 15:1 tannic acid:nucleic acid, weight/weight. In some aspects, the at least one nucleic acid can comprise DNA. [0215] In some aspects, a lipid nanoparticle can comprise a polyphenol and lipid at a specified ratio (weight/weight). [0216] In some aspects, a lipid nanoparticle, including those put forth in Table 1A and Table 1B, can comprise a polyphenol and lipid at a ratio of about 0.08:1, or about 0.1:1, or about 0.15:1, or about 0.17:1, or about 0.2:1, or about 0.22:1 or about 0.25:1, or about 0.3:1 polyphenol:lipid, weight/weight. [0217] Exemplary LNPs of the Present Disclosure [0218] The following are exemplary LNPs of the present disclosure. [0219] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% to about 50% of at least one compound of Formula (I) by moles, about 37.5% to about 56% of at least one structural lipid by moles, about 5% to about 12% of at least one phospholipid by moles, and about 1% to about 2.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 60% of at least one compound of Formula (I) by moles, about 27.5% to about 66% of at least one structural lipid by moles, about 0.1% to about 22% of at least one phospholipid by moles, and about 0.1% to about 12.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 55% of at least one compound of Formula (I) by moles, about 32.5% to about 61% of at least one structural lipid by moles, about 1% to about 17% of at least one phospholipid by moles, and about 1% to about 7.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 to about 80:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0220] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% of at least one compound of Formula (I) by moles, about 56% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 45% of at least one compound of Formula (I) by moles, about 46% to about 66% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 40% of at least one compound of Formula (I) by moles, about 51% to about 61% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0221] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 38.5% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (I) by moles, about 28.5% to about 48.5% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (I) by moles, about 33.5% to about 43.5% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 1% to about 6.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 90:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w) or about 80:1 (w/w). [0222] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 37.5% at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 2.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (I) by moles, about 27.5% to about 47.5% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 12.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (I) by moles, about 32.5% to about 42.5% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 1% to about 7.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 30:1 (w/w) to about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). [0223] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 40% of at least one compound of Formula (I) by moles, about 52.5% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 2.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 50% of at least one compound of Formula (I) by moles, about 42.5% to about 62.5% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 12.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 45% of at least one compound of Formula (I) by moles, about 47.5% to about 57.5% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 7.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 30:1 (w/w) to about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). [0224] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 45% of at least one compound of Formula (I) by moles, about 45.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 2% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 55% of at least one compound of Formula (I) by moles, about 35.5% to about 55.5% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 12% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 50% of at least one compound of Formula (I) by moles, about 40.5% to about 50.5% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0225] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 43.17% of at least one compound of Formula (I) by moles, about 43.17% of at least one structural lipid by moles, about 11.96% of at least one phospholipid by moles, and about 1.7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 33.17% to about 53.17% of at least one compound of Formula (I) by moles, about 33.17% to about 53.17% of at least one structural lipid by moles, about 1.96% to about 21.96% of at least one phospholipid by moles, and about 0.1% to about 11.7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 38.17% to about 48.17% of at least one compound of Formula (I) by moles, about 38.17% to about 48.17% of at least one structural lipid by moles, about 6.96% to about 16.96% of at least one phospholipid by moles, and about 1% to about 6.7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w) to about 90:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0226] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 45% of at least one compound of Formula (I) by moles, about 43% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 2% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 55% of at least one compound of Formula (I) by moles, about 33% to about 53% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 12% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 50% of at least one compound of Formula (I) by moles, about 38% to about 48% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 1% to about 7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w) to about 90:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0227] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 45% of at least one compound of Formula (I) by moles, about 46% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 55% of at least one compound of Formula (I) by moles, about 36% to about 56% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 50% of at least one compound of Formula (I) by moles, about 41% to about 51% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0228] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 39% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (I) by moles, about 29% to about 49% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (I) by moles, about 34% to about 44% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0229] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 41.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (I) by moles, about 31.5% to about 51.5% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (I) by moles, about 36.5% to about 46.5% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0230] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 40% of at least one compound of Formula (I) by moles, about 48.5% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 50% of at least one compound of Formula (I) by moles, about 38.5% to about 58.5% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 45% of at least one compound of Formula (I) by moles, about 43.5% to about 53.5% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w) to about 90:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0231] In some aspects, a lipid nanoparticle is provided comprising about 35% to about 50% of at least one compound of Formula (II) by moles, about 37% to about 59% of at least one structural lipid by moles, about 5% to about 10% of at least one phospholipid by moles, and about 1% to about 3% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 60% of at least one compound of Formula (II) by moles, about 27% to about 69% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 13% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 55% of at least one compound of Formula (II) by moles, about 32% to about 64% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 0.5% to about 8% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 to about 80:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0232] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% of at least one compound of Formula (II) by moles, about 59% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 45% of at least one compound of Formula (II) by moles, about 49% to about 69% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 40% of at least one compound of Formula (II) by moles, about 54% to about 64% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0233] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II) by moles, about 41.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (II) by moles, about 31.5% to about 51.5% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (II) by moles, about 36.5% to about 46.5% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0234] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II) by moles, about 39% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (II) by moles, about 29% to about 49% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (II) by moles, about 34% to about 44% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0235] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 42.5% of at least one compound of Formula (II) by moles, about 51.5% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 32.5% to about 52.5% of at least one compound of Formula (II) by moles, about 41.5% to about 61.5% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 37.5% to about 47.5% of at least one compound of Formula (II) by moles, about 46.5% to about 56.5% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 30:1 (w/w) to about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). [0236] In some aspects, a lipid nanoparticle is provided comprising about 35% to about 50% of at least one compound of Formula (II’) by moles, about 37% to about 59% of at least one structural lipid by moles, about 5% to about 10% of at least one phospholipid by moles, and about 1% to about 3% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 60% of at least one compound of Formula (II’) by moles, about 27% to about 69% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 13% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 55% of at least one compound of Formula (II’) by moles, about 32% to about 64% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 0.5% to about 8% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 to about 80:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0237] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% of at least one compound of Formula (II’) by moles, about 59% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 45% of at least one compound of Formula (II’) by moles, about 49% to about 69% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 40% of at least one compound of Formula (II’) by moles, about 54% to about 64% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0238] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II’) by moles, about 41.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (II’) by moles, about 31.5% to about 51.5% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (II’) by moles, about 36.5% to about 46.5% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0239] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II’) by moles, about 39% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (II’) by moles, about 29% to about 49% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (II’) by moles, about 34% to about 44% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0240] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 42.5% of at least one compound of Formula (II’) by moles, about 51.5% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 32.5% to about 52.5% of at least one compound of Formula (II’) by moles, about 41.5% to about 61.5% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the present disclosure provides a lipid nanoparticle comprising about 37.5% to about 47.5% of at least one compound of Formula (II’) by moles, about 46.5% to about 56.5% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one RNA molecule (e.g. mRNA molecule). In some aspects, the mRNA molecule further comprises a 5’-CAP. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 30:1 (w/w) to about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). [0241] In some aspects, the nucleic acid molecule is a DNA molecule. Thus, the present disclosure provides a lipid nanoparticle comprising about 35% to about 50% of at least one compound of Formula (I) by moles, about 37.5% to about 56% of at least one structural lipid by moles, about 5% to about 12% of at least one phospholipid by moles, and about 1% to about 2.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 60% of at least one compound of Formula (I) by moles, about 27.5% to about 66% of at least one structural lipid by moles, about 0.1% to about 22% of at least one phospholipid by moles, and about 0.1% to about 12.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 55% of at least one compound of Formula (I) by moles, about 32.5% to about 61% of at least one structural lipid by moles, about 1% to about 17% of at least one phospholipid by moles, and about 1% to about 7.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 to about 80:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0242] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% of at least one compound of Formula (I) by moles, about 56% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 45% of at least one compound of Formula (I) by moles, about 46% to about 66% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 40% of at least one compound of Formula (I) by moles, about 51% to about 61% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0243] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 38.5% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (I) by moles, about 28.5% to about 48.5% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (I) by moles, about 33.5% to about 43.5% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 1% to about 6.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 90:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w) or about 80:1 (w/w). [0244] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 37.5% at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 2.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (I) by moles, about 27.5% to about 47.5% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 12.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (I) by moles, about 32.5% to about 42.5% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 1% to about 7.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 30:1 (w/w) to about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). [0245] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 40% of at least one compound of Formula (I) by moles, about 52.5% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 2.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 50% of at least one compound of Formula (I) by moles, about 42.5% to about 62.5% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 12.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 45% of at least one compound of Formula (I) by moles, about 47.5% to about 57.5% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 7.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 30:1 (w/w) to about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). [0246] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 45% of at least one compound of Formula (I) by moles, about 45.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 2% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 55% of at least one compound of Formula (I) by moles, about 35.5% to about 55.5% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 12% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 50% of at least one compound of Formula (I) by moles, about 40.5% to about 50.5% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0247] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 43.17% of at least one compound of Formula (I) by moles, about 43.17% of at least one structural lipid by moles, about 11.96% of at least one phospholipid by moles, and about 1.7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 33.17% to about 53.17% of at least one compound of Formula (I) by moles, about 33.17% to about 53.17% of at least one structural lipid by moles, about 1.96% to about 21.96% of at least one phospholipid by moles, and about 0.1% to about 11.7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 38.17% to about 48.17% of at least one compound of Formula (I) by moles, about 38.17% to about 48.17% of at least one structural lipid by moles, about 6.96% to about 16.96% of at least one phospholipid by moles, and about 1% to about 6.7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w) to about 90:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0248] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 45% of at least one compound of Formula (I) by moles, about 43% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 2% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 55% of at least one compound of Formula (I) by moles, about 33% to about 53% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 12% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 50% of at least one compound of Formula (I) by moles, about 38% to about 48% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 1% to about 7% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w) to about 90:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0249] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 45% of at least one compound of Formula (I) by moles, about 46% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 55% of at least one compound of Formula (I) by moles, about 36% to about 56% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 50% of at least one compound of Formula (I) by moles, about 41% to about 51% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0250] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 39% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (I) by moles, about 29% to about 49% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (I) by moles, about 34% to about 44% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0251] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (I) by moles, about 41.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (I) by moles, about 31.5% to about 51.5% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (I) by moles, about 36.5% to about 46.5% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0252] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 40% of at least one compound of Formula (I) by moles, about 48.5% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 50% of at least one compound of Formula (I) by moles, about 38.5% to about 58.5% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 35% to about 45% of at least one compound of Formula (I) by moles, about 43.5% to about 53.5% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6.5% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w) to about 90:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0253] In some aspects, a lipid nanoparticle is provided comprising about 35% to about 50% of at least one compound of Formula (II) by moles, about 37% to about 59% of at least one structural lipid by moles, about 5% to about 10% of at least one phospholipid by moles, and about 1% to about 3% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 60% of at least one compound of Formula (II) by moles, about 27% to about 69% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 13% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 55% of at least one compound of Formula (II) by moles, about 32% to about 64% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 0.5% to about 8% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 to about 80:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0254] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% of at least one compound of Formula (II) by moles, about 59% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 45% of at least one compound of Formula (II) by moles, about 49% to about 69% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 40% of at least one compound of Formula (II) by moles, about 54% to about 64% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0255] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II) by moles, about 41.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (II) by moles, about 31.5% to about 51.5% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (II) by moles, about 36.5% to about 46.5% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0256] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II) by moles, about 39% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (II) by moles, about 29% to about 49% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (II) by moles, about 34% to about 44% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0257] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 42.5% of at least one compound of Formula (II) by moles, about 51.5% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 32.5% to about 52.5% of at least one compound of Formula (II) by moles, about 41.5% to about 61.5% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 37.5% to about 47.5% of at least one compound of Formula (II) by moles, about 46.5% to about 56.5% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 30:1 (w/w) to about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). [0258] In some aspects, a lipid nanoparticle is provided comprising about 35% to about 50% of at least one compound of Formula (II’) by moles, about 37% to about 59% of at least one structural lipid by moles, about 5% to about 10% of at least one phospholipid by moles, and about 1% to about 3% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 60% of at least one compound of Formula (II’) by moles, about 27% to about 69% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 13% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 55% of at least one compound of Formula (II’) by moles, about 32% to about 64% of at least one structural lipid by moles, about 1% to about 15% of at least one phospholipid by moles, and about 0.5% to about 8% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 to about 80:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 80:1 (w/w). [0259] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 35% of at least one compound of Formula (II’) by moles, about 59% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 25% to about 45% of at least one compound of Formula (II’) by moles, about 49% to about 69% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 30% to about 40% of at least one compound of Formula (II’) by moles, about 54% to about 64% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0260] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II’) by moles, about 41.5% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (II’) by moles, about 31.5% to about 51.5% of at least one structural lipid by moles, about 0.1% to about 17.5% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (II’) by moles, about 36.5% to about 46.5% of at least one structural lipid by moles, about 1% to about 12.5% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w) to about 70:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0261] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 50% of at least one compound of Formula (II’) by moles, about 39% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 40% to about 60% of at least one compound of Formula (II’) by moles, about 29% to about 49% of at least one structural lipid by moles, about 0.1% to about 20% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 45% to about 55% of at least one compound of Formula (II’) by moles, about 34% to about 44% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w) to about 60:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0262] In some aspects, a lipid nanoparticle comprising at least one nucleic acid can comprise about 42.5% of at least one compound of Formula (II’) by moles, about 51.5% of at least one structural lipid by moles, about 5% of at least one phospholipid by moles, and about 1% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 32.5% to about 52.5% of at least one compound of Formula (II’) by moles, about 41.5% to about 61.5% of at least one structural lipid by moles, about 0.1% to about 15% of at least one phospholipid by moles, and about 0.1% to about 11% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the present disclosure provides a lipid nanoparticle comprising about 37.5% to about 47.5% of at least one compound of Formula (II’) by moles, about 46.5% to about 56.5% of at least one structural lipid by moles, about 1% to about 10% of at least one phospholipid by moles, and about 1% to about 6% of at least one PEGylated lipid by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In one aspect, the at least one DNA molecule is a DoggyBone DNA molecule. In some aspects, the at least one DNA molecule is a DNA nanoplasmid. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 30:1 (w/w) to about 50:1 (w/w). In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 40:1 (w/w). [0263] In some aspects, a lipid nanoparticle is provided comprising about 42.5% of at least one compound of Formula (I) by moles, about 45.75% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, about 1.5% of at least one PEGylated lipid by moles, and about 0.25% of at least one targeting ligand comprising GalNac by moles, wherein the at least one nucleic acid comprises at least one DNA molecule and at least one RNA molecule. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 50:1 (w/w). [0264] In some aspects, a lipid nanoparticle is provided comprising about 35% of at least one compound of Formula (I) by moles, about 52.75% of at least one structural lipid by moles, about 10% of at least one phospholipid by moles, about 2% of at least one PEGylated lipid by moles, and about 0.25% of at least one targeting ligand comprising GalNac by moles, wherein the at least one nucleic acid comprises at least one DNA molecule and at least one RNA molecule. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). [0265] In some aspects, a lipid nanoparticle is provided comprising about 40% of at least one compound of Formula (II) by moles, about 50.2% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, about 2% of at least one PEGylated lipid by moles, and about 0.3% of at least one targeting ligand comprising GalNac by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). In some aspects of the preceding LNPs, the lipid nanoparticle further comprises tannic acid in a ratio of tannic acid to lipid of about 0.15, or about 2, or about 0.22. [0266] In some aspects, a lipid nanoparticle is provided comprising about 40% of at least one compound of Formula (II’) by moles, about 50.2% of at least one structural lipid by moles, about 7.5% of at least one phospholipid by moles, about 2% of at least one PEGylated lipid by moles, and about 0.3% of at least one targeting ligand comprising GalNac by moles, wherein the at least one nucleic acid comprises at least one DNA molecule. In some aspects, the ratio of lipid to nucleic acid in the nanoparticle can be about 60:1 (w/w). In some aspects of the preceding LNPs, the lipid nanoparticle further comprises tannic acid in a ratio of tannic acid to lipid of about 0.15, or about 2, or about 0.22. Compositions of the Present Disclosure [0267] The present disclosure provides compositions comprising at least one lipid nanoparticle of the present disclosure. The compositions of the present disclosure can further comprise any number of additional components. Pharmaceutical Compositions of the Present Disclosure [0268] In some aspects, the present disclosure provides a pharmaceutical composition comprising at least one lipid nanoparticle of the present disclosure. In some aspects, the present disclosure provides a pharmaceutical composition comprising at least one first nanoparticle of the present disclosure and at least one second nanoparticle of the present disclosure, wherein the at least one first nanoparticle comprises at least one nucleic acid molecule encoding at least one transposase, wherein the at least one second nanoparticle comprises at least one nucleic acid molecule encoding at least one transposon. In some aspects, the at least one nucleic acid molecule encoding at least one transposase can be an RNA molecule (e.g. mRNA molecule) and the at least one nucleic acid molecule encoding at least one transposon can be a DNA molecule (e.g. a DoggyBone DNA molecule or a DNA nanoplasmid). [0269] In some aspects, the present disclosure provides a composition comprising at least one cell that has been contacted by at least one nanoparticle of the present disclosure. In some aspects, the present disclosure provides a composition comprising at least one cell that has been genetically modified using at least one nanoparticle of the present disclosure. In some aspects, the present disclosure provides a composition comprising at least one cell that has been genetically modified using any method of the present disclosure. [0270] In some aspects, the present disclosure provides a pharmaceutical composition comprising at least one cell that has been contacted by at least one nanoparticle of the present disclosure. In some aspects, the present disclosure provides a pharmaceutical composition comprising at least one cell that has been genetically modified using at least one nanoparticle of the present disclosure. In some aspects, the present disclosure provides a pharmaceutical composition comprising at least one cell that has been genetically modified using any method of the present disclosure. Methods of the Present Disclosure [0271] The present disclosure provides a method of delivering at least one nucleic acid to at least one cell comprising contacting the at least one cell with at least one composition of the present disclosure. The present disclosure provides a method of delivering at least one nucleic acid to at least one cell comprising contacting the at least one cell with at least one nanoparticle of the present disclosure. [0272] In all methods, compositions and kits of the present disclosure, at least one cell can be a liver cell. A liver cell can include, but is not limited to, a hepatocyte, a hepatic stellate cell, Kupffer cell or a liver sinusoidal endothelial cell. [0273] In some aspects of any methods of the present disclosure, a cell can be in vivo, ex vivo or in vitro. In some aspects, any of the methods of the present disclosure can be applied in vivo, ex vivo or in vitro. [0274] The present disclosure provides a method of genetically modifying at least one cell comprising contacting the at least one cell with at least one composition of the present disclosure. The present disclosure provides a method of genetically modifying at least one cell comprising contacting the at least one cell with at least one nanoparticle of the present disclosure. [0275] In some aspects, genetically modifying a cell can comprise delivering at least one exogenous nucleic acid to the cell such that the cell expresses at least one protein that the cell otherwise would not normally express, or such that the at least one cell expresses at least one protein at a level that is higher than the level that the cell would otherwise normally express the at least one protein, or such that the cell expresses at least one protein at a level that is lower than the level that the cell would otherwise normally express. In some aspects, genetically modifying a cell can comprise delivering at least one exogenous nucleic to the cell such that at least one exogenous nucleic acid is integrated into the genome of the at least one cell. [0276] In some aspects, the methods of the present disclosure can yield a plurality of cells, wherein at least about 1%, or at least about 2%, or at least about 3%, or at least about 4%, or at least about 5%, or at least 10%, or at least 15%, or at least 20%, or at least 25%, or at least 30%, or at least 35%, or at least 40%, or at least 45%, or at least 50%, or at least 55%, or at least 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 95%, or at least about 99% of the cell in the plurality express at least one protein that was encoded in at least one nucleic acid that was delivered to the plurality of cells via a nanoparticle of the present disclosure. [0277] The present disclosure provides a method of treating at least one disease in a subject, the method comprising administering to the subject at least one therapeutically effective amount of at least one composition of the present disclosure comprising at least one nucleic acid encoding a therapeutic protein. In some embodiments, the subject is human. The terms “subject” and “patient” are used interchangeably herein. The present disclosure provides a method of treating at least one disease in a subject, the method comprising administering a therapeutically effective amount of at least one nanoparticle of the present disclosure comprising at least one nucleic acid encoding a therapeutic protein. [0278] Without wishing to be bound by theory, it is hypothesized that the LNP compositions of the present disclosure target liver cells more effectively than other cells, thus reducing off- target effects associated with other delivery compositions. [0279] In some embodiments, the LNP compositions provided herein that comprise a targeting ligand result in less cytokine release than the same LNP composition not comprising the targeting ligand. Cytokine release may be measured using any suitable method know in the art or described herein. For example, cytokine levels may be determined in the blood of a subject receiving the LNP composition comprising the targeting ligand using enzyme-linked immunosorbent assays (ELISAs). The cytokine levels may then be compared to pre-treatement baseline levels. [0280] The present disclosure provides a method of treating at least one disease in a subject, the method comprising administering a therapeutically effective amount of cells, wherein the cells have been contacted by at least one nanoparticle of the present disclosure comprising at least one nucleic acid encoding a therapeutic protein. The present disclosure provides a method of treating at least one disease in a subject, the method comprising administering a therapeutically effective amount of cells, wherein the cells have been genetically modified using the compositions and/or methods of the present disclosure.In some aspects, the at least one disease can be a malignant disease, including, but not limited to, cancer. In some aspects, the at least one disease can be a metabolic liver disorder (MLD). In some aspects, the at least one disease can be a urea cycle disorder (UCD). An MLD and/or UCD can include, but is not limited to, N-Acetylglutamate Synthetase (NAGS) Deficiency, Carbamoylphosphate Synthetase I Deficiency (CPSI Deficiency), Ornithine Transcarbamylase (OTC) Deficiency, Argininosuccinate Synthetase Deficiency (ASSD) (Citrullinemia I), Citrin Deficiency (Citrullinemia II), Argininosuccinate Lyase Deficiency (Argininosuccinic Aciduria), Arginase Deficiency (Hyperargininemia), Ornithine Translocase Deficiency (HHH Syndrome), methylmalonic acidemia (MMA) or any combination thereof. [0281] Methods of the disclosure may be used to treat a disease or disorder by use of a therapeutic transgene encoding for an exogenous nucleic acid sequence or exogenous amino acid sequence. In such methods, the transgene is delivered to a target cell to replace or repair a mutated gene. Diseases that may be treated with such methods are generally caused by a mutation in a gene that results in no protein being expressed or non-functional proteins being expressed. Examples of therapeutic transgenes that can be delivered using the compositions disclosed herein include: Beta-Thalassemia (HBB T87Q, BCL11A shRNA, IGF2BP1), Sickle Cell Disease (HBB T87Q, BCL11A shRNA, IGF2BP1), Hemophilia A (Factor VIII), Hemophilia B (Factor IX), X-linked Severe Combined Immunodeficiency (Interleukin 2 receptor gamma (IL2RG)), Hypophosphatasia (Tissue Non-specific Alkaline Phosphatase (TNAP)), Osteopetrosis (TCIRG1), Glycogen Storage Disease Type II (Pompe Disease) (Alpha Glucosidase (GAA)), Alpha-Galactosidase A Deficiency (Fabry disease) (Alpha- galactosidase A (GLA)), Mucopolysaccharidosis Type I (MPS I) (Alpha-L-iduronidase (IDUA)), Mucopolysaccharidosis Type II (MPS II) (Iduronate 2-sulfatase (IDS)), Mucopolysaccharidosis Type IIIA (MPS IIIA) (sulfoglycosamine-sulfohydrolase (SGSH)), Mucopolysaccharidosis Type IIIB (MPS IIIB) (N-alpha-acetylglucosaminidase (NAGLU)), Mucopolysaccharidosis Type IV A (MPS IVA) (Morquio) (N-acetylgalactosamine-6-sulfate sulfatase (GALNS)), Mucopolysaccharidosis Type IV B (MPS IVB) Beta-galactosidase (GLB1 (Beta-galactosidase (GLB1)), Cholesteryl Ester Storage Disease (CESD) (Lysosomal acid lipase (LIPA)), Cystinosis (Cystinosin lysosomal cystine transporter (CTNS)), X-linked chronic granulomatous disease (X-CGD) (CYBB), Wiskott-Aldrich Syndrome (WAS) (WAS), X-linked Adrenoleukodystrophy (X-ALD) (ABCD1), Metachromatic leukopdystrophy (MLD) (ARSA), Phenylketonuria (PAH), Methylmalonic academia (MMUT), Propionic Acidemia (PCCA, PCCB), Retinitis Pigmentosa (RPE65), Usher Syndrome (MYO7A), and Gaucher Disease (GBA). [0282] Methods of the present disclosure can optionally further comprise co-administration or combination therapy for treating such diseases or disorders, wherein the administering of any composition or pharmaceutical composition disclosed herein, further comprises administering, before concurrently, and/or after, at least one chemotherapeutic agent (e.g., an alkylating agent, an a mitotic inhibitor, a radiopharmaceutical). Nucleic Acid Molecules [0283] In some aspects, a nucleic acid molecule can be an RNA molecule. Thus, in some aspects, a lipid nanoparticle can comprise at least one RNA molecule. The at least one RNA molecule can be encapsulated within the lipid nanoparticle. In some aspects, an RNA molecule can be an mRNA molecule. In some aspects, a lipid nanoparticle can comprise at least one mRNA molecule. The mRNA molecule can be encapsulated within the lipid nanoparticle. [0284] In some aspects, a nucleic acid molecule can be a synthetic nucleic acid molecule. In some aspects, a nucleic acid molecule can be a non-naturally occurring nucleic acid molecule. In some aspects, a non-naturally occurring nucleic acid molecule can comprise at least one non-naturally occurring nucleotide. The at least one non-naturally occurring nucleotide can be any non-naturally occurring nucleotide known in the art. In some aspects, a nucleic acid molecule can be a modified nucleic acid molecule. In some aspects, a modified nucleic acid molecule can comprise at least one modified nucleotide. The at least one modified nucleotide can be any modified nucleic acid known in the art. [0285] In some aspects, an mRNA molecule can be capped using any method and/or capping moiety known in the art. An mRNA molecule can be capped with m7G(5’)ppp(5’)G moiety. A m7G(5’)ppp(5’)G moiety is also referred to herein as a “Cap0”. An mRNA molecule can be capped with a CleanCap® moiety. A CleanCap® moiety can comprise a m7G(5')ppp(5')(2'OMeA) (CleanCap® AG) moiety. A CleanCap® moiety can comprise a m7G(5')ppp(5')(2'OMeG) (CleanCap® GG) moiety. An mRNA molecule can be capped with an anti-reverse cap analog (ARCA®) moiety. An ARCA® moiety can comprise a m7(3’-O- methyl)G(5’)ppp(5’)G moiety. An mRNA molecule can be capped with a CleanCap® 3’OMe moiety (CleanCap®+ARCA®). [0286] In some aspects, an mRNA molecule can comprise at least one modified nucleic acid. [0287] The at least one modified nucleic acid can comprise 5-methoxyuridine (5moU). In some aspects, at least about 5%, or at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, at least about 90%, or at least about 95%, or at least about 99% of the uridine bases in an mRNA molecule are 5-methoxyuridine bases. In some aspects, all of the uridine bases in an mRNA molecule are 5-methoxyuridine bases. Without wishing to be bound by theory, 5-methoxyuridine can improve protein expression and reduce immunogenicity (see Li et al., Bioconjugate Chem.2016, 27, 3, 849-853 and Vaidyanathan et al. Molecular Therapy – Nucleic Acids, 2018, 12, 530-542). [0288] In some aspects, an mRNA molecule can comprise at least one modified nucleic acid. [0289] The at least one modified nucleic acid can comprise N1-methylpseudouridine (me¹Ψ). In some aspects, at least about 5%, or at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, at least about 90%, or at least about 95%, or at least about 99% of the uridine bases in an mRNA N₁-methylpseudouridine bases. In some aspects, all of the uridine bases in an mRNA molecule are N1-methylpseudouridine bases. Without wishing to be bound by theory, N₁-methylpseudouridine can improve protein expression (see Li et al., Bioconjugate Chem.2016, 27, 3, 849-853). [0290] In some aspects, an mRNA molecule can comprise at least one modified nucleic acid. [0291] The at least one modified nucleic acid can comprise pseudouridine (Ψ). In some aspects, at least about 5%, or at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, at least about 90%, or at least about 95%, or at least about 99% of the uridine bases in an mRNA pseudouridine bases. In some aspects, all of the uridine bases in an mRNA molecule are pseudouridine bases. Without wishing to be bound by theory, pseudouridine can improve protein expression and reduce immunogenicity (see Li et al., Bioconjugate Chem. 2016, 27, 3, 849-853 and Vaidyanathan et al. Molecular Therapy – Nucleic Acids, 2018, 12, 530-542). [0292] In some aspects, an mRNA molecule can comprise at least one modified nucleic acid. [0293] The at least one modified nucleic acid can comprise 5-methylcytidine (5-MeC). In some aspects, at least about 5%, or at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, at least about 90%, or at least about 95%, or at least about 99% of the cytidine bases in an mRNA 5-MeC bases. In some aspects, all of the cytidine bases in an mRNA molecule are 5-MeC bases. [0294] In some aspects, a nucleic acid molecule can comprise a DNA molecule. Thus, in some aspects, a lipid nanoparticle can comprise a DNA molecule. In some aspects, the DNA molecule can be a circular DNA molecule, such as, but not limited to, a DNA plasmid or DNA nanoplasmid. Thus, in some aspects, a lipid nanoparticle can comprise a circular DNA molecule. In some aspects, a lipid nanoparticle can comprise a Doggybone DNA molecule. In some aspects, a lipid nanoparticle can comprise a DNA plasmid. In some aspects, a lipid nanoparticle can comprise a DNA nanoplasmid. In some aspects, a DNA molecule can be a linearized DNA molecule, such as, but not limited to, a linearized DNA plasmid or a linearized DNA nanoplasmid. [0295] A DNA plasmid or DNA nanoplasmid can comprise can be at least about 0.25 kb, or at least about 0.5 kb, or at least about 0.75 kb, or at least about 1.0 kb, or at least about 1.25 kb, or at least about 1.5 kb, or at least about 1.75 kb, or at least about 2.0 kb, or at least about 2.25 kb, or at least about 2.5 kb, or at least about 2.75 kb, or at least about 3.0 kb, or at least about 3.25 kb, or at least about 3.5 kb, or at least about 3.75 kb, or at least about 4.0 kb, or at least about 4.25 kb, or at least about 4.5 kb, or at least about 4.75 kb, or at least about 5.0 kb, or at least about 5.25 kb, or at least about 5.5 kb, or at least about 5.75 kb, or at least about 6.0 kb, or at least about 6.25 kb, or at least about 6.5 kb, or at least about 6.75 kb, or at least about 7.0 kb, or at least about 7.25 kb, or at least about 7.5 kb, or at least about 7.75 kb, or at least about 8.0 kb, or at least about 8.25 kb, or at least about 8.5 kb, or at least about 8.75 kb, or at least about 9.0 kb, or at least about 9.25 kb, or at least about 9.5 kb, or at least about 9.75 kb, or at least about 10.0 kb, or at least about 10.25 kb, or at least about 10.5 kb, or at least about 10.75 kb, or at least about 11.0 kb, or at least about 11.25 kb, or at least about 11.5 kb, or at least about 11.75 kb, or at least about 12 kb, or at least about 12.25 kb, or at least about 12.5 kb, or at least about 12.75 kb, or at least about 13.0 kb, or at least about 13.25 kb, or at least about 13.5 kb, or at least about 13.75 kb, or at least about 14.0 kb, or at least about 14.25 kb, or at least about 14.5 kb, or at least about 14.75 kb or at least about 15.0 kb in length. [0296] In some aspects, a nucleic acid molecule formulated in a lipid nanoparticle of the present disclosure can comprise at least one transgene sequence. In some aspects, a transgene sequence can comprise a nucleotide sequence encoding at least one therapeutic protein. In some aspects, a transgene sequence can comprise a nucleotide sequence encoding at least one transposase. In some aspects, a transgene sequence can comprise a nucleotide sequence encoding at least one transposon. In some aspects, a transposon can comprise a nucleotide sequence encoding at least one therapeutic protein. In some aspects, a transposon can comprise a nucleotide sequence encoding at least one therapeutic protein and at least one protomer sequence, wherein the at least one therapeutic protein is operatively linked to the at least one promoter sequence. [0297] In some aspects, the lipid nanoparticles of the present disclosure can be produced using a microfluidic-mixing platform. In some aspects, the microfluidic-mixing platform can be a non-turbulent microfluidic mixing platform. [0298] In some aspects, a microfluidic-mixing platform can produce the lipid nanoparticles of the present disclosure by combining a miscible solvent phase comprising the lipid components of the nanoparticle and an aqueous phase comprising the lipid nanoparticle cargo (e.g. nucleic acid, DNA, mRNA, etc.) using a microfluidic device. In some aspects, the miscible solvent phase and the aqueous phase are mixed in the microfluidic device under laminar flow conditions that do not allow for immediate mixing of the two phases. As the two phases move under laminar flow in a microfluidic channel, microscopic features in the channel can allow for controlled, homogenous mixing to produce the lipid nanoparticles of the present disclosure. [0299] In some aspects, the microfluidic-mixing platform can include, but are not limited to the NanoAssemblr® Spark (Precision NanoSystems), the NanoAssemblr® Ignite™ (Precision NanoSystems), the NanoAssemblr® Benchtop (Precision NanoSystems), the NanoAssemblr® Blaze (Precision NanoSystems) or the NanoAssemblr® GMP System (Precision NanoSystems). [0300] In some aspects, the lipid nanoparticles of the present disclosure can be produced using a microfluidic-mixing platform, wherein the microfluidic mixing platform mixes at a rate of at least about 2.5 ml/min, or at least about 5 ml/min, or at least about 7.5 ml/min, or at least about 10 ml/min, or at least about 12.5 ml/min, or at least about 15 ml/min, or at least about 17.5 ml/min, or at least about 20 ml/min, or at least about 22.5 ml/min, or at least about 25 ml/min, or at least about 27.5 ml/min, or at least about 30 ml/min. [0301] In some aspects, the lipid nanoparticles of the present disclosure can be produced using a microfluidic-mixing platform, wherein the microfluidic mixing platform mixes a miscible solvent phase and an aqueous phase at a ratio of about 10:1, or about 9:1, or about 8:1, or about 7:1, or about 6:1, or about 5:1, or about 4:1, or about 3:1, or about 2:1, or about 1:1, or about 1:2, or about 1:3, or about 1:4, or about 1:5, or about 1:6, or about 1:7, or about 1:8, or about 1:9, or about 1:10, solvent:aqueous, v:v. piggyBac ITR sequences [0302] In some aspects, a nucleic acid can comprise a piggyBac ITR sequence. In some aspects, a nucleic acid can comprise a first piggyBac ITR sequence and a second piggyBac ITR sequence. [0303] In some aspects, a piggyBac ITR sequence can comprise any piggyBac ITR sequence known in the art. [0304] In some aspects of the methods of the present disclosure, a piggyBac ITR sequence, such as a first piggyBac ITR sequence and/or a second piggyBac ITR sequence in an AAV piggyBac transposon can comprise, consist essentially of, or consist of a Sleeping Beauty transposon ITR, a Helraiser transposon ITR, a Tol2 transposon ITR, a TcBuster transposon ITR or any combination thereof. Transposition systems [0305] In some aspects, a nucleic acid can comprise a transposon or a nanotransposon comprising: a first nucleic acid sequence comprising: (a) a first inverted terminal repeat (ITR) or a sequence encoding a first ITR, (b) a second ITR or a sequence encoding a second ITR, and (c) an intra-ITR sequence or a sequence encoding an intra-ITR, wherein the intra-ITR sequence comprises a transposon sequence or a sequence encoding a transposon. [0306] In some aspects, a nucleic acid can comprise a transposon or a nanotransposon comprising: a first nucleic acid sequence comprising: (a) a first inverted terminal repeat (ITR) or a sequence encoding a first ITR, (b) a second ITR or a sequence encoding a second ITR, and (c) an intra-ITR sequence or a sequence encoding an intra-ITR, wherein the intra-ITR sequence comprises a transposon sequence or a sequence encoding a transposon, and a second nucleic acid sequence comprising an inter-ITR sequence or a sequence encoding an inter-ITR, wherein the length of the inter-ITR sequence is equal to or less than 700 nucleotides. [0307] The transposon or nanotransposon of the present disclosure can be a piggyBac™ (PB) transposon. In some aspects when the transposon is a PB transposon, the transposase is a piggyBac™ (PB) transposase a piggyBac-like (PBL) transposase or a Super piggyBac™ (SPB) transposase. Preferably, the sequence encoding the SPB transposase is an mRNA sequence. [0308] Non-limiting examples of PB transposons and PB, PBL and SPB transposases are described in detail in U.S. Patent No.6,218,182; U.S. Patent No.6,962,810; U.S. Patent No. 8,399,643 and PCT Publication No. WO 2010/099296, each of which is incorporated herein by reference in its entirety for examples of transposons and transposases that may be used in the compositions and methods described herein. [0309] The PB, PBL and SPB transposases recognize transposon-specific inverted terminal repeat sequences (ITRs) on the ends of the transposon, and inserts the contents between the ITRs at the sequence 5’-TTAT-3’ within a chromosomal site (a TTAT target sequence) or at the sequence 5’-TTAA-3’ within a chromosomal site (a TTAA target sequence). The target sequence of the PB or PBL transposon can comprise or consist of 5’-CTAA-3’, 5’-TTAG-3’, 5’-ATAA-3’, 5’-TCAA-3’, 5’AGTT-3’, 5’-ATTA-3’, 5’-GTTA-3’, 5’-TTGA-3’, 5’-TTTA- 3’, 5’-TTAC-3’, 5’-ACTA-3’, 5’-AGGG-3’, 5’-CTAG-3’, 5’-TGAA-3’, 5’-AGGT-3’, 5’- ATCA-3’, 5’-CTCC-3’, 5’-TAAA-3’, 5’-TCTC-3’, 5’TGAA-3’, 5’-AAAT-3’, 5’-AATC-3’, 5’-ACAA-3’, 5’-ACAT-3’, 5’-ACTC-3’, 5’-AGTG-3’, 5’-ATAG-3’, 5’-CAAA-3’, 5’- CACA-3’, 5’-CATA-3’, 5’-CCAG-3’, 5’-CCCA-3’, 5’-CGTA-3’, 5’-GTCC-3’, 5’-TAAG-3’, 5’-TCTA-3’, 5’-TGAG-3’, 5’-TGTT-3’, 5’-TTCA-3’5’-TTCT-3’ and 5’-TTTT-3’. The PB or PBL transposon system has no payload limit for the genes of interest that can be included between the ITRs. [0310] Exemplary amino acid sequences for one or more PB, PBL and SPB transposases are disclosed in U.S. Patent No.6,218,185; U.S. Patent No.6,962,810 and U.S. Patent No. 8,399,643, each of which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein. In a preferred aspect, the PB transposase comprises or consists of an amino acid sequence at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 1. [0311] The PB or PBL transposase can comprise or consist of an amino acid sequence having an amino acid substitution at two or more, at three or more or at each of positions 30, 165, 282, and/or 538 of the sequence of SEQ ID NO: 1. The transposase can be a SPB transposase that comprises or consists of the amino acid sequence of the sequence of SEQ ID NO: 1 wherein the amino acid substitution at position 30 can be a substitution of a valine (V) for an isoleucine (I), the amino acid substitution at position 165 can be a substitution of a serine (S) for a glycine (G), the amino acid substitution at position 282 can be a substitution of a valine (V) for a methionine (M), and the amino acid substitution at position 538 can be a substitution of a lysine (K) for an asparagine (N). In a preferred aspect, the SPB transposase comprises or consists of an amino acid sequence at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 2. [0312] In certain aspects wherein the transposase comprises the above-described mutations at positions 30, 165, 282 and/or 538, the PB, PBL and SPB transposases can further comprise an amino acid substitution at one or more of positions 3, 46, 82, 103, 119, 125, 177, 180, 185, 187, 200, 207, 209, 226, 235, 240, 241, 243, 258, 296, 298, 311, 315, 319, 327, 328, 340, 421, 436, 456, 470, 486, 503, 552, 570 and 591 of the sequence of SEQ ID NO: 1 or SEQ ID NO: 2 are described in more detail in PCT Publication No. WO 2019/173636 and No. WO 2020/051374, each of which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein. [0313] In a preferred aspect, the PB transposase comprises or consists of an amino acid sequence at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 3. [0314] The PB or PBL transposase can comprise or consist of an amino acid sequence having an amino acid substitution at two or more, at three or more or at each of positions 29, 164, 281, and/or 537 of the sequence of SEQ ID NO: 3. The transposase can be a SPB transposase that comprises or consists of the amino acid sequence of the sequence of SEQ ID NO: 3 wherein the amino acid substitution at position 29 can be a substitution of a valine (V) for an isoleucine (I), the amino acid substitution at position 164 can be a substitution of a serine (S) for a glycine (G), the amino acid substitution at position 281 can be a substitution of a valine (V) for a methionine (M), and the amino acid substitution at position 537 can be a substitution of a lysine (K) for an asparagine (N). In a preferred aspect, the SPB transposase comprises or consists of an amino acid sequence at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 4. [0315] In certain aspects wherein the transposase comprises the above-described mutations at positions 29, 164, 281, and/or 537, the PB, PBL and SPB transposases can further comprise an amino acid substitution at one or more of positions 2, 45, 81, 102, 118, 124, 176, 179, 184, 186, 199, 206, 208, 225, 234, 239, 240, 242, 257, 295, 297, 310, 314, 318, 326, 327, 339, 420, 435, 455, 469, 485, 502, 551, 569 and 590 of the sequence of SEQ ID NO: 3 or SEQ ID NO: 4 are described in more detail in PCT Publication No. WO 2019/173636 and No. WO 2020/051374, each of which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein.. [0316] The PB, PBL or SPB transposases can be isolated or derived from an insect, vertebrate, crustacean or urochordate as described in more detail in PCT Publication No. WO 2019/173636 and No. WO 2020/051374, each of which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein. In preferred aspects, the PB, PBL or SPB transposases is isolated or derived from the insect Trichoplusia ni (GenBank Accession No. AAA87375) or Bombyx mori (GenBank Accession No. BAD11135). [0317] A hyperactive PB or PBL transposase is a transposase that is more active than the naturally occurring variant from which it is derived. In a preferred aspect, a hyperactive PB or PBL transposase is isolated or derived from Bombyx mori or Xenopus tropicalis. Examples of hyperactive PB or PBL transposases are disclosed in U.S. Patent No.6,218,185; U.S. Patent No.6,962,810, U.S. Patent No.8,399,643 and WO 2019/173636, each of which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein. A list of hyperactive amino acid substitutions is disclosed in U.S. Patent No.10,041,077, which is incorporated herein by reference in its entirety for examples of amino acid substitutions that may be introduced into the transposases disclosed herein. A transposon or nanotransposon of the present disclosure can be a Sleeping Beauty transposon. In some aspects, when the transposon is a Sleeping Beauty transposon, the transposase is a Sleeping Beauty transposase (for example as disclosed in U.S. Patent No.9,228,180 which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein) or a hyperactive Sleeping Beauty (SB100X) transposase. [0318] In some aspects, the PB or PBL transposase is integration deficient. An integration deficient PB or PBL transposase is a transposase that can excise its corresponding transposon, but that integrates the excised transposon at a lower frequency than a corresponding wild type transposase. Examples of integration deficient PB or PBL transposases are disclosed in U.S. Patent No.6,218,185; U.S. Patent No.6,962,810, U.S. Patent No.8,399,643 and WO 2019/173636, each of which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein. A list of integration deficient amino acid substitutions is disclosed in US patent No.10,041,077 which is incorporated herein by reference in its entirety for examples of amino acid substitutions that may be introduced into the transposases described herein. [0319] In some aspects, the PB or PBL transposase is fused to a nuclear localization signal. Examples of PB or PBL transposases fused to a nuclear localization signal are disclosed in U.S. Patent No.6,218,185; U.S. Patent No.6,962,810, U.S. Patent No.8,399,643 and WO 2019/173636, each of which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein. [0320] A transposon or nanotransposon of the present disclosure can be a Sleeping Beauty transposon. In some aspects, when the transposon is a Sleeping Beauty transposon, the transposase is a Sleeping Beauty transposase (for example as disclosed in U.S. Patent No. 9,228,180, which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein) or a hyperactive Sleeping Beauty (SB100X) transposase. [0321] A transposon or nanotransposon of the present disclosure can be a Helraiser transposon. An exemplary Helraiser transposon includes Helibat1. In some aspects, when the transposon is a Helraiser transposon, the transposase is a Helitron transposase (for example, as disclosed in WO 2019/173636, which is incorporated herein by reference in its entirety for examples of transposons that may be used in the compositions and methods described herein). [0322] A transposon or nanotransposon of the present disclosure can be a Tol2 transposon. In some aspects, when the transposon is a Tol2 transposon, the transposase is a Tol2 transposase (for example, as disclosed in WO 2019/173636, which is incorporated herein by reference in its entirety for examples of transposons and nanotransponsons that may be used in the compositions and methods described herein). [0323] A transposon or nanotransposon of the present disclosure can be a TcBuster transposon. In some aspects, when the transposon is a TcBuster transposon, the transposase is a TcBuster transposase or a hyperactive TcBuster transposase (for example, as disclosed in WO 2019/173636). The TcBuster transposase can comprise or consist of a naturally occurring amino acid sequence or a non-naturally occurring amino acid sequence. The polynucleotide encoding a TcBuster transposase can comprise or consist of a naturally occurring nucleic acid sequence or a non-naturally occurring nucleic acid sequence. [0324] In some aspects, a mutant TcBuster transposase comprises one or more sequence variations when compared to a wild type TcBuster transposase as described in more detail in PCT Publications No. WO 2019/173636 and No. WO 2020/051374, each of which is incorporated herein by reference in its entirety for examples of transposases that may be used in the compositions and methods described herein [0325] The cell delivery compositions (e.g., transposons) disclosed herein can comprise a nucleic acid molecule encoding a therapeutic protein or therapeutic agent. Examples of therapeutic proteins include those disclosed in PCT Publications No. WO 2019/173636 and No. WO 2020/051374, each of which is incorporated herein by reference in its entirety for examples of therapeutic proteins that may be used in the compositions and methods described herein. Gene editing systems [0326] The present disclosure provides a gene editing composition and/or a cell comprising the gene editing composition. The gene editing composition can comprise a nanoparticle comprising a nucleic acid, wherein the nucleic acid comprises a sequence encoding a DNA binding domain and a sequence encoding a nuclease protein or a nuclease domain thereof. The sequence encoding a nuclease protein or the sequence encoding a nuclease domain thereof can comprise a DNA sequence, an RNA sequence, or a combination thereof. The nuclease or the nuclease domain thereof can comprise one or more of a CRISPR/Cas protein, a Transcription Activator-Like Effector Nuclease (TALEN), a Zinc Finger Nuclease (ZFN), and an endonuclease. [0327] The nuclease or the nuclease domain thereof can comprise a nuclease-inactivated Cas (dCas) protein and an endonuclease. The endonuclease can comprise a Clo051 nuclease or a nuclease domain thereof. The gene editing composition can comprise a fusion protein. The fusion protein can comprise a nuclease-inactivated Cas9 (dCas9) protein and a Clo051 nuclease or a Clo051 nuclease domain. In some aspects, the fusion protein can further comprise at least one nuclear localization signal (NLS). In some aspects, the fusion protein can further comprise at least two NLSs. The gene editing composition can further comprise a guide sequence. The guide sequence can comprise an RNA sequence. [0328] A transgene can comprise a nucleic sequence encoding a small, Cas9 (Cas9) operatively-linked to an effector. The disclosure provides a fusion protein comprising, consisting essentially of or consisting of a DNA localization component and an effector molecule, wherein the effector comprises a small, Cas9 (Cas9). A small Cas9 construct of the disclosure can comprise an effector comprising a type IIS endonuclease. [0329] A transgene can comprise a nucleic sequence encoding an inactivated, small, Cas9 (dSaCas9) operatively-linked to an effector. A transgene can comprise a nucleic sequence encoding a fusion protein comprising, consisting essentially of or consisting of a DNA localization component and an effector molecule, wherein the effector comprises a small, inactivated Cas9 (dSaCas9). A small, inactivated Cas9 (dSaCas9) construct of the disclosure can comprise an effector comprising a type IIS endonuclease. [0330] A transgene can comprise a nucleic sequence encoding an inactivated Cas9 (dCas9) operatively-linked to an effector. A transgene can comprise a nucleic sequence encoding a fusion protein comprising, consisting essentially of or consisting of a DNA localization component and an effector molecule, wherein the effector comprises an inactivated Cas9 (dCas9). An inactivated Cas9 (dCas9) construct of the disclosure can comprise an effector comprising a type IIS endonuclease. [0331] The dCas9 can be isolated or derived from Streptoccocus pyogenes. The dCas9 can comprise a dCas9 with substitutions at amino acid positions 10 and 840, which inactivate the catalytic site. In some aspects, these substitutions are D10A and H840A. [0332] A cell comprising the gene editing composition can express the gene editing composition stably or transiently. Preferably, the gene editing composition is expressed transiently. The guide RNA can comprise a sequence complementary to a target sequence within a genomic DNA sequence. The target sequence within a genomic DNA sequence can be a target sequence within a safe harbor site of a genomic DNA sequence. [0333] Gene editing compositions, including Cas-CLOVER, and methods of using these compositions for gene editing are described in detail in U.S. Patent Publication Nos. 2017/0107541, 2017/0114149, 2018/0187185 and U.S. Patent No.10,415,024, each of which is incorporated herein by reference in its entirety for examples of gene editing compositions that may be used in the compositions and methods described herein. In some aspects, a Cas- CLOVER protein can comprise, consist essentially of, or consist of an amino acid sequence at least 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% (or any percentage in between) identical to SEQ ID NO: 5 or 6. [0334] Accordingly, the present disclosure provides any of the lipid nanoparticle compositions described herein, wherein the lipid nanoparticle comprises at least one genomic editing composition, wherein the at least one genomic editing composition comprises: a) a nucleic acid molecule comprising a nucleic acid sequence encoding a fusion protein, wherein the fusion protein comprises (i) an inactivated Cas9 (dCas9) protein or an inactivated nuclease domain thereof, (ii) a Clo051 protein or a nuclease domain thereof; and b) at least one gRNA molecule. In some aspects, the fusion protein can further comprise at least one NLS. In some aspects, the at least one genomic editing composition can comprise at least two species of gRNA molecules. Formulations, Dosages and Modes of Administration [0335] The present disclosure provides formulations, dosages and methods for administration of the compositions described herein. [0336] The disclosed compositions and pharmaceutical compositions can further comprise at least one of any suitable auxiliary, such as, but not limited to, diluent, binder, stabilizer, buffers, salts, lipophilic solvents, preservative, adjuvant or the like. Pharmaceutically acceptable auxiliaries are preferred. Non-limiting examples of, and methods of preparing such sterile solutions are well known in the art, such as, but limited to, Gennaro, Ed., Remington's Pharmaceutical Sciences, 18th Edition, Mack Publishing Co. (Easton, Pa.) 1990 and in the “Physician's Desk Reference”, 52nd ed., Medical Economics (Montvale, N.J.) 1998. Pharmaceutically acceptable carriers can be routinely selected that are suitable for the mode of administration, solubility and/or stability of the composition as well known in the art or as described herein. [0337] For example, the disclosed LNP compositions of the present disclosure can further comprise a diluent. In some compositions, the diluent can be phosphate buffered saline (“PBS”). [0338] Non-limiting examples of pharmaceutical excipients and additives suitable for use include proteins, peptides, amino acids, lipids, and carbohydrates (e.g., sugars, including monosaccharides, di-, tri-, tetra-, and oligosaccharides; derivatized sugars, such as alditols, aldonic acids, esterified sugars and the like; and polysaccharides or sugar polymers), which can be present singly or in combination, comprising alone or in combination 1-99.99% by weight or volume. Non-limiting examples of protein excipients include serum albumin, such as human serum albumin (HSA), recombinant human albumin (rHA), gelatin, casein, and the like. Representative amino acid/protein components, which can also function in a buffering capacity, include alanine, glycine, arginine, betaine, histidine, glutamic acid, aspartic acid, cysteine, lysine, leucine, isoleucine, valine, methionine, phenylalanine, aspartame, and the like. One preferred amino acid is glycine. [0339] The compositions can also include a buffer or a pH-adjusting agent; typically, the buffer is a salt prepared from an organic acid or base. Representative buffers include organic acid salts, such as salts of citric acid, ascorbic acid, gluconic acid, carbonic acid, tartaric acid, succinic acid, acetic acid, or phthalic acid; Tris, tromethamine hydrochloride, or phosphate buffers. Preferred buffers are organic acid salts, such as citrate. In some aspects, the buffer can include sucrose. [0340] Many known and developed modes can be used for administering therapeutically effective amounts of the compositions or pharmaceutical compositions disclosed herein. Non- limiting examples of modes of administration include bolus, buccal, infusion, intrarticular, intrabronchial, intraabdominal, intracapsular, intracartilaginous, intracavitary, intracelial, intracerebellar, intracerebroventricular, intracolic, intracervical, intragastric, intrahepatic, intralesional, intramuscular, intramyocardial, intranasal, intraocular, intraosseous, intraosteal, intrapelvic, intrapericardiac, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intraretinal, intraspinal, intrasynovial, intrathoracic, intrauterine, intratumoral, intravenous, intravesical, oral, parenteral, rectal, sublingual, subcutaneous, transdermal or vaginal means. [0341] A composition of the disclosure can be prepared for use for parenteral (subcutaneous, intramuscular or intravenous) or any other administration particularly in the form of liquid solutions or suspensions; for use in vaginal or rectal administration particularly in semisolid forms, such as, but not limited to, creams and suppositories; for buccal, or sublingual administration, such as, but not limited to, in the form of tablets or capsules; or intranasally, such as, but not limited to, the form of powders, nasal drops or aerosols or certain agents; or transdermally, such as not limited to a gel, ointment, lotion, suspension or patch delivery system with chemical enhancers such as dimethyl sulfoxide to either modify the skin structure or to increase the drug concentration in the transdermal patch (Junginger, et al. In “Drug Permeation Enhancement;” Hsieh, D. S., Eds., pp.59-90 (Marcel Dekker, Inc. New York 1994,), or applications of electric fields to create transient transport pathways, such as electroporation, or to increase the mobility of charged drugs through the skin, such as iontophoresis, or application of ultrasound, such as sonophoresis (U.S. Pat. Nos.4,309,989 and 4,767,402) (the above publications and patents being entirely incorporated herein by reference). [0342] For parenteral administration, any composition disclosed herein can be formulated as a solution, suspension, emulsion, particle, powder, or lyophilized powder in association, or separately provided, with a pharmaceutically acceptable parenteral vehicle. Formulations for parenteral administration can contain as common excipients sterile water or saline, polyalkylene glycols, such as polyethylene glycol, oils of vegetable origin, hydrogenated naphthalenes and the like. Aqueous or oily suspensions for injection can be prepared by using an appropriate emulsifier or humidifier and a suspending agent, according to known methods. Agents for injection can be a non-toxic, non-orally administrable diluting agent, such as aqueous solution, a sterile injectable solution or suspension in a solvent. As the usable vehicle or solvent, water, Ringer's solution, isotonic saline, etc. are allowed; as an ordinary solvent or suspending solvent, sterile involatile oil can be used. For these purposes, any kind of involatile oil and fatty acid can be used, including natural or synthetic or semisynthetic fatty oils or fatty acids; natural or synthetic or semisynthtetic mono- or di- or tri-glycerides. Parental administration is known in the art and includes, but is not limited to, conventional means of injections, a gas pressured needle-less injection device as described in U.S. Pat. No. 5,851,198, and a laser perforator device as described in U.S. Pat. No.5,839,446. [0343] For pulmonary administration, preferably, a composition or pharmaceutical composition described herein is delivered in a particle size effective for reaching the lower airways of the lung or sinuses. The composition or pharmaceutical composition can be delivered by any of a variety of inhalation or nasal devices known in the art for administration of a therapeutic agent by inhalation. These devices capable of depositing aerosolized formulations in the sinus cavity or alveoli of a patient include metered dose inhalers, nebulizers (e.g., jet nebulizer, ultrasonic nebulizer), dry powder generators, sprayers, and the like. All such devices can use formulations suitable for the administration for the dispensing of a composition or pharmaceutical composition described herein in an aerosol. Such aerosols can be comprised of either solutions (both aqueous and non-aqueous) or solid particles. In a metered dose inhaler (MDI), a propellant, a composition or pharmaceutical composition described herein, and any excipients or other additives are contained in a canister as a mixture including a liquefied compressed gas. Actuation of the metering valve releases the mixture as an aerosol. A more detailed description of pulmonary administration, formulations and related devices is disclosed in PCT Publication No. WO 2019/049816. [0344] For absorption through mucosal surfaces, compositions include an emulsion comprising a plurality of submicron particles, a mucoadhesive macromolecule, a bioactive peptide, and an aqueous continuous phase, which promotes absorption through mucosal surfaces by achieving mucoadhesion of the emulsion particles (U.S. Pat. No.5,514,670). Mucous surfaces suitable for application of the emulsions of the disclosure can include corneal, conjunctival, buccal, sublingual, nasal, vaginal, pulmonary, stomachic, intestinal, and rectal routes of administration. Formulations for vaginal or rectal administration, e.g., suppositories, can contain as excipients, for example, polyalkyleneglycols, vaseline, cocoa butter, and the like. Formulations for intranasal administration can be solid and contain as excipients, for example, lactose or can be aqueous or oily solutions of nasal drops. For buccal administration, excipients include sugars, calcium stearate, magnesium stearate, pregelinatined starch, and the like (U.S. Pat. No.5,849,695). A more detailed description of mucosal administration and formulations is disclosed in PCT Publication No. WO 2019/049816. [0345] For transdermal administration, a composition or pharmaceutical composition disclosed herein is encapsulated in a delivery device, such as a liposome or polymeric nanoparticles, microparticle, microcapsule, or microspheres (referred to collectively as microparticles unless otherwise stated). A number of suitable devices are known, including microparticles made of synthetic polymers, such as polyhydroxy acids, such as polylactic acid, polyglycolic acid and copolymers thereof, polyorthoesters, polyanhydrides, and polyphosphazenes, and natural polymers, such as collagen, polyamino acids, albumin and other proteins, alginate and other polysaccharides, and combinations thereof (U.S. Pat. No. 5,814,599). A more detailed description of transdermal administration, formulations and suitable devices is disclosed in PCT Publication No. WO 2019/049816. [0346] It can be desirable to deliver the disclosed compounds to the subject over prolonged periods of time, for example, for periods of one week to one year from a single administration. Various slow release, depot or implant dosage forms can be utilized. [0347] Suitable dosages are well known in the art. See, e.g., Wells et al., eds., Pharmacotherapy Handbook, 2nd Edition, Appleton and Lange, Stamford, Conn. (2000); PDR Pharmacopoeia, Tarascon Pocket Pharmacopoeia 2000, Deluxe Edition, Tarascon Publishing, Loma Linda, Calif. (2000); Nursing 2001 Handbook of Drugs, 21st edition, Springhouse Corp., Springhouse, Pa., 2001; Health Professional's Drug Guide 2001, ed., Shannon, Wilson, Stang, Prentice-Hall, Inc, Upper Saddle River, N.J. Preferred doses can optionally include about 0.1-99 and/or 100-500 mg/kg/administration, or any range, value or fraction thereof, or to achieve a serum concentration of about 0.1-5000 μg/ml serum concentration per single or multiple administration, or any range, value or fraction thereof. A preferred dosage range for the compositions or pharmaceutical compositions disclosed herein is from about 1 mg/kg, up to about 3, about 6 or about 12 mg/kg of body weight of the subject. [0348] Alternatively, the dosage administered can vary depending upon known factors, such as the pharmacodynamic characteristics of the particular agent, and its mode and route of administration; age, health, and weight of the recipient; nature and extent of symptoms, kind of concurrent treatment, frequency of treatment, and the effect desired. [0349] As a non-limiting example, treatment of humans or animals can be provided as a one- time or periodic dosage of the compositions or pharmaceutical compositions disclosed herein about 0.1 to 100 mg/kg or any range, value or fraction thereof per day, on at least one of day 1-40, or, alternatively or additionally, at least one of week 1-52, or, alternatively or additionally, at least one of 1-20 years, or any combination thereof, using single, infusion or repeated doses. [0350] In aspects where the compositions to be administered to a subject in need thereof are modified cells as disclosed herein, the cells can be administered between about 1x10³ and 1x10¹⁵ cells; 1x10³ and 1x10¹⁵ cells, about 1x10⁴ and 1x10¹² cells; about 1x10⁵ and 1x10¹⁰ cells; about 1x10⁶ and 1x10⁹ cells; about 1x10⁶ and 1x10⁸ cells; about 1x10⁶ and 1x10⁷ cells; or about 1x10⁶ and 25x10⁶ cells. In an aspect the cells are administered between about 5x10⁶ and 25x10⁶ cells. [0351] A more detailed description of pharmaceutically acceptable excipients, formulations, dosages and methods of administration of the disclosed compositions and pharmaceutical compositions is disclosed in PCT Publication No. WO 2019/04981. [0352] The disclosure provides the use of a disclosed composition or pharmaceutical composition for the treatment of a disease or disorder in a cell, tissue, organ, animal, or subject, as known in the art or as described herein, using the disclosed compositions and pharmaceutical compositions, e.g., administering or contacting the cell, tissue, organ, animal, or subject with a therapeutic effective amount of the composition or pharmaceutical composition. In an aspect, the subject is a mammal. Preferably, the subject is human. The terms “subject” and “patient” are used interchangeably herein. [0353] The disclosure provides a method for modulating or treating at least one malignant disease or disorder in a cell, tissue, organ, animal or subject. Non-limiting examples of a malignant disease or disorder include cancer and liver diseases or disorders. [0354] Any method can comprise administering an effective amount of any composition or pharmaceutical composition disclosed herein to a cell, tissue, organ, animal or subject in need of such modulation, treatment or therapy. Such a method can optionally further comprise co- administration or combination therapy for treating such diseases or disorders, wherein the administering of any composition or pharmaceutical composition disclosed herein, further comprises administering, before concurrently, and/or after, at least one chemotherapeutic agent (e.g., an alkylating agent, an a mitotic inhibitor, a radiopharmaceutical). [0355] In some aspects, the subject does not develop graft vs. host (GvH) and/or host vs. graft (HvG) following administration. In an aspect, the administration is systemic. Systemic administration can be any means known in the art and described in detail herein. Preferably, systemic administration is by an intravenous injection or an intravenous infusion. In an aspect, the administration is local. Local administration can be any means known in the art and described in detail herein. Preferably, local administration is by intra-tumoral injection or infusion, intraspinal injection or infusion, intracerebroventricular injection or infusion, intraocular injection or infusion, or intraosseous injection or infusion. [0356] In some aspects, the therapeutically effective dose is a single dose. In some aspects, the single dose is one of at least 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or any number of doses in between that are manufactured simultaneously. In some aspects, where the composition is autologous cells or allogeneic cells, the dose is an amount sufficient for the cells to engraft and/or persist for a sufficient time to treat the disease or disorder. [0357] In some aspects of the methods of treatment described herein, the treatment can be modified or terminated. Specifically, in aspects where the composition used for treatment comprises an inducible proapoptotic polypeptide, apoptosis may be selectively induced in the cell by contacting the cell with an induction agent. A treatment may be modified or terminated in response to, for example, a sign of recovery or a sign of decreasing disease severity/progression, a sign of disease remission/cessation, and/or the occurrence of an adverse event. In some aspects, the method comprises the step of administering an inhibitor of the induction agent to inhibit modification of the cell therapy, thereby restoring the function and/or efficacy of the cell therapy (for example, when a sign or symptom of the disease reappear or increase in severity and/or an adverse event is resolved). Construction of Nucleic Acids [0358] The isolated nucleic acids of the disclosure can be made using (a) recombinant methods, (b) synthetic techniques, (c) purification techniques, and/or (d) combinations thereof, as well-known in the art. [0359] The nucleic acids can conveniently comprise sequences in addition to a polynucleotide of the present disclosure. For example, a multi-cloning site comprising one or more endonuclease restriction sites can be inserted into the nucleic acid to aid in isolation of the polynucleotide. Also, translatable sequences can be inserted to aid in the isolation of the translated polynucleotide of the disclosure. For example, a hexa-histidine marker sequence provides a convenient means to purify the proteins of the disclosure. The nucleic acid of the disclosure, excluding the coding sequence, is optionally a vector, adapter, or linker for cloning and/or expression of a polynucleotide of the disclosure. [0360] Additional sequences can be added to such cloning and/or expression sequences to optimize their function in cloning and/or expression, to aid in isolation of the polynucleotide, or to improve the introduction of the polynucleotide into a cell. Use of cloning vectors, expression vectors, adapters, and linkers is well known in the art. (See, e.g., Ausubel, supra; or Sambrook, supra). Recombinant Methods for Constructing Nucleic Acids [0361] The isolated nucleic acid compositions of this disclosure, such as RNA, cDNA, genomic DNA, or any combination thereof, can be obtained from biological sources using any number of cloning methodologies known to those of skill in the art. In some aspects, oligonucleotide probes that selectively hybridize, under stringent conditions, to the polynucleotides of the present disclosure are used to identify the desired sequence in a cDNA or genomic DNA library. The isolation of RNA, and construction of cDNA and genomic libraries are well known to those of ordinary skill in the art. (See, e.g., Ausubel, supra; or Sambrook, supra). Nucleic Acid Screening and Isolation Methods [0362] A cDNA or genomic library can be screened using a probe based upon the sequence of a polynucleotide of the disclosure. Probes can be used to hybridize with genomic DNA or cDNA sequences to isolate homologous genes in the same or different organisms. Those of skill in the art will appreciate that various degrees of stringency of hybridization can be employed in the assay; and either the hybridization or the wash medium can be stringent. As the conditions for hybridization become more stringent, there must be a greater degree of complementarity between the probe and the target for duplex formation to occur. The degree of stringency can be controlled by one or more of temperature, ionic strength, pH and the presence of a partially denaturing solvent, such as formamide. For example, the stringency of hybridization is conveniently varied by changing the polarity of the reactant solution through, for example, manipulation of the concentration of formamide within the range of 0% to 50%. The degree of complementarity (sequence identity) required for detectable binding will vary in accordance with the stringency of the hybridization medium and/or wash medium. The degree of complementarity will optimally be 100%, or 70-100%, or any range or value therein. However, it should be understood that minor sequence variations in the probes and primers can be compensated for by reducing the stringency of the hybridization and/or wash medium. [0363] Methods of amplification of RNA or DNA are well known in the art and can be used according to the disclosure without undue experimentation, based on the teaching and guidance presented herein. [0364] Known methods of DNA or RNA amplification include, but are not limited to, polymerase chain reaction (PCR) and related amplification processes (see, e.g., U.S. Pat. Nos. 4,683,195, 4,683,202, 4,800,159, 4,965,188, to Mullis, et al.; 4,795,699 and 4,921,794 to Tabor, et al; 5,142,033 to Innis; 5,122,464 to Wilson, et al.; 5,091,310 to Innis; 5,066,584 to Gyllensten, et al; 4,889,818 to Gelfand, et al; 4,994,370 to Silver, et al; 4,766,067 to Biswas; 4,656,134 to Ringold) and RNA mediated amplification that uses anti-sense RNA to the target sequence as a template for double-stranded DNA synthesis (U.S. Pat. No.5,130,238 to Malek, et al, with the tradename NASBA), the entire contents of which references are incorporated herein by reference. (See, e.g., Ausubel, supra; or Sambrook, supra.) [0365] For instance, polymerase chain reaction (PCR) technology can be used to amplify the sequences of polynucleotides of the disclosure and related genes directly from genomic DNA or cDNA libraries. PCR and other in vitro amplification methods can also be useful, for example, to clone nucleic acid sequences that code for proteins to be expressed, to make nucleic acids to use as probes for detecting the presence of the desired mRNA in samples, for nucleic acid sequencing, or for other purposes. Examples of techniques sufficient to direct persons of skill through in vitro amplification methods are found in Berger, supra, Sambrook, supra, and Ausubel, supra, as well as Mullis, et al., U.S. Pat. No.4,683,202 (1987); and Innis, et al., PCR Protocols A Guide to Methods and Applications, Eds., Academic Press Inc., San Diego, Calif. (1990). Commercially available kits for genomic PCR amplification are known in the art. See, e.g., Advantage-GC Genomic PCR Kit (Clontech). Additionally, e.g., the T4 gene 32 protein (Boehringer Mannheim) can be used to improve yield of long PCR products. Synthetic Methods for Constructing Nucleic Acids [0366] The isolated nucleic acids of the disclosure can also be prepared by direct chemical synthesis by known methods (see, e.g., Ausubel, et al., supra). Chemical synthesis generally produces a single-stranded oligonucleotide, which can be converted into double-stranded DNA by hybridization with a complementary sequence, or by polymerization with a DNA polymerase using the single strand as a template. One of skill in the art will recognize that while chemical synthesis of DNA can be limited to sequences of about 100 or more bases, longer sequences can be obtained by the ligation of shorter sequences. Recombinant Expression Cassettes [0367] The disclosure further provides recombinant expression cassettes comprising a nucleic acid of the disclosure. A nucleic acid sequence of the disclosure can be used to construct a recombinant expression cassette that can be introduced into at least one desired host cell. A recombinant expression cassette will typically comprise a polynucleotide of the disclosure operably linked to transcriptional initiation regulatory sequences that will direct the transcription of the polynucleotide in the intended host cell. Both heterologous and non- heterologous (i.e., endogenous) promoters can be employed to direct expression of the nucleic acids of the disclosure. [0368] In some aspects, isolated nucleic acids that serve as promoter, enhancer, or other elements can be introduced in the appropriate position (upstream, downstream or in the intron) of a non-heterologous form of a polynucleotide of the disclosure so as to up or down regulate expression of a polynucleotide of the disclosure. For example, endogenous promoters can be altered in vivo or in vitro by mutation, deletion and/or substitution. Expression Vectors and Host Cells [0369] The disclosure also relates to vectors that include isolated nucleic acid molecules of the disclosure and host cells that are genetically engineered with the recombinant vectors, as is well known in the art. See, e.g., Sambrook, et al., supra; Ausubel, et al., supra, each entirely incorporated herein by reference. [0370] The polynucleotides can optionally be joined to a vector containing a selectable marker for propagation in a host. Generally, a plasmid vector is introduced in a precipitate, such as a calcium phosphate precipitate, or in a complex with a charged lipid. If the vector is a virus, it can be packaged in vitro using an appropriate packaging cell line and then transduced into host cells. [0371] The DNA insert should be operatively linked to an appropriate promoter. The expression constructs will further contain sites for transcription initiation, termination and, in the transcribed region, a ribosome binding site for translation. The coding portion of the mature transcripts expressed by the constructs will preferably include a translation initiating at the beginning and a termination codon (e.g., UAA, UGA or UAG) appropriately positioned at the end of the mRNA to be translated, with UAA and UAG preferred for mammalian or eukaryotic cell expression. [0372] Expression vectors will preferably but optionally include at least one selectable marker. Such markers include, e.g., but are not limited to, ampicillin, zeocin (Sh bla gene), puromycin (pac gene), hygromycin B (hygB gene), G418/Geneticin (neo gene), DHFR (encoding Dihydrofolate Reductase and conferring resistance to Methotrexate), mycophenolic acid, or glutamine synthetase (GS, U.S. Pat. Nos.5,122,464; 5,770,359; 5,827,739), blasticidin (bsd gene), resistance genes for eukaryotic cell culture as well as ampicillin, zeocin (Sh bla gene), puromycin (pac gene), hygromycin B (hygB gene), G418/Geneticin (neo gene), kanamycin, spectinomycin, streptomycin, carbenicillin, bleomycin, erythromycin, polymyxin B, or tetracycline resistance genes for culturing in E. coli and other bacteria or prokaryotics (the above patents are entirely incorporated hereby by reference). Appropriate culture mediums and conditions for the above-described host cells are known in the art. Suitable vectors will be readily apparent to the skilled artisan. Introduction of a vector construct into a host cell can be effected by calcium phosphate transfection, DEAE-dextran mediated transfection, cationic lipid-mediated transfection, electroporation, transduction, infection or other known methods. Such methods are described in the art, such as Sambrook, supra, Chapters 1-4 and 16-18; Ausubel, supra, Chapters 1, 9, 13, 15, 16. [0373] Expression vectors will preferably but optionally include at least one selectable cell surface marker for isolation of cells modified by the compositions and methods of the disclosure. Selectable cell surface markers of the disclosure comprise surface proteins, glycoproteins, or group of proteins that distinguish a cell or subset of cells from another defined subset of cells. Preferably the selectable cell surface marker distinguishes those cells modified by a composition or method of the disclosure from those cells that are not modified by a composition or method of the disclosure. Such cell surface markers include, e.g., but are not limited to, “cluster of designation” or “classification determinant” proteins (often abbreviated as “CD”) such as a truncated or full length form of CD19, CD271, CD34, CD22, CD20, CD33, CD52, or any combination thereof. Cell surface markers further include the suicide gene marker RQR8 (Philip B et al. Blood.2014 Aug 21; 124(8):1277-87). [0374] Expression vectors will preferably but optionally include at least one selectable drug resistance marker for isolation of cells modified by the compositions and methods of the disclosure. Selectable drug resistance markers of the disclosure may comprise wild-type or mutant Neo, DHFR, TYMS, FRANCF, RAD51C, GCS, MDR1, ALDH1, NKX2.2, or any combination thereof. [0375] Those of ordinary skill in the art are knowledgeable in the numerous expression systems available for expression of a nucleic acid molecule encoding a protein of the disclosure. Definitions [0376] As used throughout the disclosure, the singular forms “a,” “and,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a method” includes a plurality of such methods and reference to “a dose” includes reference to one or more doses and equivalents thereof known to those skilled in the art, and so forth. [0377] The term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, “about” can mean within 1 or more standard deviations. Alternatively, “about” can mean a range of up to 20%, or up to 10%, or up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, preferably within 5-fold, and more preferably within 2-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated the term “about” meaning within an acceptable error range for the particular value should be assumed. [0378] In the chemical formulas shown herein, the marking indicates the position where a functional group bonds to another portion of a molecule. Definitions of specific functional groups and chemical terms are described in more detail below. [0379] Certain compounds of the present disclosure may exist in particular geometric or stereoisomeric forms. The present disclosure contemplates all such compounds, including cis- and trans-isomers, R- and S-enantiomers, diastereomers, (D)-isomers, (L)-isomers, the racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the disclosure. Additional asymmetric carbon atoms may be present in a substituent such as an alkyl group. All such isomers, as well as mixtures thereof, are intended to be included in this disclosure. [0380] Isomeric mixtures containing any of a variety of isomer ratios may be utilized in accordance with the present disclosure. For example, where only two isomers are combined, mixtures containing 50:50, 60:40, 70:30, 80:20, 90:10, 95:5, 96:4, 97:3, 98:2, 99:1, or 100:0 isomer ratios are all contemplated by the present disclosure. Those of ordinary skill in the art will readily appreciate that analogous ratios are contemplated for more complex isomer mixtures. [0381] If, for instance, a particular enantiomer of a compound of the present disclosure is desired, it may be prepared by asymmetric synthesis, or by derivation with a chiral auxiliary, where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers. Alternatively, where the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts are formed with an appropriate optically-active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art, and subsequent recovery of the pure enantiomers. [0382] One of ordinary skill in the art will appreciate that the synthetic methods, as described herein, utilize a variety of protecting groups. By the term "protecting group," as used herein, it is meant that a particular functional moiety, e.g., O, S, or N, is temporarily blocked so that a reaction can be carried out selectively at another reactive site in a multifunctional compound. In certain embodiments, a protecting group reacts selectively in good yield to give a protected substrate that is stable to the projected reactions; the protecting group should be selectively removable in good yield by readily available, preferably non-toxic reagents that do not attack the other functional groups; the protecting group forms an easily separable derivative (more preferably without the generation of new stereogenic centers); and the protecting group has a minimum of additional functionality to avoid further sites of reaction. As detailed herein, oxygen, sulfur, nitrogen, and carbon protecting groups may be utilized. [0383] The term "aliphatic," as used herein, includes both saturated and unsaturated, straight chain (i.e., unbranched), branched, acyclic, cyclic, or polycyclic aliphatic hydrocarbons, which are optionally substituted with one or more functional groups. As will be appreciated by one of ordinary skill in the art, "aliphatic" is intended herein to include, but is not limited to, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl moieties. Thus, as used herein, the term "alkyl" includes straight, branched and cyclic alkyl groups. An analogous convention applies to other generic terms such as "alkenyl," "alkynyl," and the like. Furthermore, as used herein, the terms "alkyl," "alkenyl," "alkynyl," and the like encompass both substituted and unsubstituted groups. In certain embodiments, as used herein, "lower alkyl" is used to indicate those alkyl groups (cyclic, acyclic, substituted, unsubstituted, branched or unbranched) having 1-6 carbon atoms. [0384] In certain embodiments, the alkyl, alkenyl, and alkynyl groups contain 1-18 aliphatic carbon atoms. In certain embodiments, the alkyl, alkenyl, and alkynyl groups contain 1-15 aliphatic carbon atoms. In certain other embodiments, the alkyl, alkenyl, and alkynyl groups contain 1-10 aliphatic carbon atoms. In yet other embodiments, the alkyl, alkenyl, and alkynyl groups contain 1-8 aliphatic carbon atoms. In still other embodiments, the alkyl, alkenyl, and alkynyl groups contain 1-6 aliphatic carbon atoms. In yet other embodiments, the alkyl, alkenyl, and alkynyl groups contain 1-4 carbon atoms. Illustrative aliphatic groups thus include, but are not limited to, for example, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, --CH2-cyclopropyl, vinyl, allyl, n-butyl, sec-butyl, isobutyl, tert-butyl, cyclobutyl, --CH₂-cyclobutyl, n-pentyl, sec-pentyl, isopentyl, tert-pentyl, cyclopentyl, --CH₂- cyclopentyl, n-hexyl, sec-hexyl, cyclohexyl, --CH₂-cyclohexyl moieties and the like, which again, may bear one or more substituents. Alkenyl groups include, but are not limited to, for example, ethenyl, propenyl, butenyl, 1-methyl-2-buten-1-yl, and the like. Representative alkynyl groups include, but are not limited to, ethynyl, 2-propynyl (propargyl), 1-propynyl, and the like. [0385] The term "alkyl" as used herein refers to saturated, straight- or branched-chain aliphatic groups having from 1 to 18 carbon atoms, As such, "alkyl" encompasses C1, C2, C3, C₄, C₅, C₆, C₇, C₈, C₉, C₁₀, C₁₁ and C₁₂ groups. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, n-pentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, n-decyl, n-undecyl, and dodecyl. [0386] The term “alkylene” refers to a divalent alkyl radical. Any of the above mentioned monovalent alkyl groups may be an alkylene by abstraction of a second hydrogen atom from the alkyl. As herein defined, alkylene may also be a C1-C18 alkylene. An alkylene may further be a C1-C12 alkylene. Typical alkylene groups include, but are not limited to, -CH2-, - CH(CH₃)-, -C(CH₃)₂-, -CH₂CH₂-, -CH₂CH(CH₃)-, -CH₂C(CH₃)₂-, -CH₂CH₂CH₂-, - CH2CH2CH2CH2-, and the like. [0387] The term "alkenyl" refers to an unsaturated straight or, when applicable, branched chain aliphatic group with one or more carbon-carbon double bonds, having from 2 to 18 carbon atoms. As such, "alkenyl" encompasses C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, C₁₀, C₁₁ and C₁₂ groups. Alkenyl groups include, for example, ethenyl, propenyl, butenyl, 1-methyl-2-buten-1- yl, and the like. [0388] The term "alkynyl" refers to an unsaturated straight or, when applicable, branched chain aliphatic group with one or more carbon-carbon triple bonds, having from 2 to 18 carbon atoms. As such, "alkynyl" encompasses C₂, C₃, C₄, C₅, C₆, C₇, C₈, C₉, C₁₀, C₁₁ and C₁₂ groups. Representative alkynyl groups include ethynyl, 2-propynyl (propargyl), 1-propynyl, and the like. [0389] As used herein, the term "aryl" group is a C6 - C14 aromatic moiety comprising one to three aromatic rings, which is optionally substituted. As such, "aryl" includes C₆, C₇, C₈, C₉, C10, C11, C12 C13, and C14 cyclic hydrocarbon groups. An exemplary aryl group is a C6-C10 aryl group. Particular aryl groups include, without limitation, phenyl, naphthyl, anthracenyl, and fluorenyl. [0390] As used herein, the term "cycloalkyl" as employed herein includes saturated and partially unsaturated cyclic hydrocarbon groups having 3 to 12 carbons. As such, "cycloalkyl" includes C₃, C₄, C₅, C₆, C₇, C₈, C₉, C₁₀, C₁₁ and C₁₂ cyclic hydrocarbon groups. Representative cycloalkyl groups include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. [0391] As used herein, the term “hydroxyalkyl” refers to -alkyl-OH or an alkyl chain substituted with at least one -OH. [0392] As used herein, the term “halo” or “halogen” refers to fluoro, chloro, bromo and iodo. [0393] It will be understood that the compounds of any one of the Formulae disclosed herein and any pharmaceutically acceptable salts thereof, comprise stereoisomers, mixtures of stereoisomers, polymorphs of all isomeric forms of said compounds. [0394] The term "independently selected" is used herein to indicate that the R groups can be identical or different. [0395] The term "substituted," whether preceded by the term "optionally" or not, and "substituent," as used herein, refer to the ability, as appreciated by one skilled in this art, to change one functional group for another functional group provided that the valency of all atoms is maintained. When more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. The substituents may also be further substituted (e.g., an aryl group substituent may have another substituent off it, such as another aryl group, which is further substituted with fluorine at one or more positions). [0396] The disclosure provides isolated or substantially purified polynucleotide or protein compositions. An "isolated" or "purified" polynucleotide or protein, or biologically active portion thereof, is substantially or essentially free from components that normally accompany or interact with the polynucleotide or protein as found in its naturally occurring environment. Thus, an isolated or purified polynucleotide or protein is substantially free of other cellular material or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. Optimally, an "isolated" polynucleotide is free of sequences (optimally protein encoding sequences) that naturally flank the polynucleotide (i.e., sequences located at the 5' and 3' ends of the polynucleotide) in the genomic DNA of the organism from which the polynucleotide is derived. For example, in various aspects, the isolated polynucleotide can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb, or 0.1 kb of nucleotide sequence that naturally flank the polynucleotide in genomic DNA of the cell from which the polynucleotide is derived. A protein that is substantially free of cellular material includes preparations of protein having less than about 30%, 20%, 10%, 5%, or 1% (by dry weight) of contaminating protein. When the protein of the disclosure or biologically active portion thereof is recombinantly produced, optimally culture medium represents less than about 30%, 20%, 10%, 5%, or 1% (by dry weight) of chemical precursors or non-protein-of-interest chemicals. [0397] The disclosure provides fragments and variants of the disclosed DNA sequences and proteins encoded by these DNA sequences. As used throughout the disclosure, the term "fragment" refers to a portion of the DNA sequence or a portion of the amino acid sequence and hence protein encoded thereby. Fragments of a DNA sequence comprising coding sequences may encode protein fragments that retain biological activity of the native protein and hence DNA recognition or binding activity to a target DNA sequence as herein described. Alternatively, fragments of a DNA sequence that are useful as hybridization probes generally do not encode proteins that retain biological activity or do not retain promoter activity. Thus, fragments of a DNA sequence may range from at least about 20 nucleotides, about 50 nucleotides, about 100 nucleotides, and up to the full-length polynucleotide of the disclosure. [0398] Nucleic acids or proteins of the disclosure can be constructed by a modular approach including preassembling monomer units and/or repeat units in target vectors that can subsequently be assembled into a final destination vector. Polypeptides of the disclosure may comprise repeat monomers of the disclosure and can be constructed by a modular approach by preassembling repeat units in target vectors that can subsequently be assembled into a final destination vector. The disclosure provides polypeptide produced by this method as well nucleic acid sequences encoding these polypeptides. The disclosure provides host organisms and cells comprising nucleic acid sequences encoding polypeptides produced this modular approach. [0399] The term "antibody" is used in the broadest sense and specifically covers single monoclonal antibodies (including agonist and antagonist antibodies) and antibody compositions with polyepitopic specificity. It is also within the scope hereof to use natural or synthetic analogs, mutants, variants, alleles, homologs and orthologs (herein collectively referred to as “analogs”) of the antibodies hereof as defined herein. Thus, according to an aspect hereof, the term “antibody hereof” in its broadest sense also covers such analogs. Generally, in such analogs, one or more amino acid residues may have been replaced, deleted and/or added, compared to the antibodies hereof as defined herein. [0400] The term "comprising" is intended to mean that the compositions and methods include the recited elements, but do not exclude others. "Consisting essentially of” when used to define compositions and methods, shall mean excluding other elements of any essential significance to the combination when used for the intended purpose. Thus, a composition consisting essentially of the elements as defined herein would not exclude trace contaminants or inert carriers. "Consisting of shall mean excluding more than trace elements of other ingredients and substantial method steps. Aspects defined by each of these transition terms are within the scope of this disclosure. [0401] As used herein, "expression" refers to the process by which polynucleotides are transcribed into mRNA and/or the process by which the transcribed mRNA is subsequently being translated into peptides, polypeptides, or proteins. If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell. [0402] “Gene expression” refers to the conversion of the information, contained in a gene, into a gene product. A gene product can be the direct transcriptional product of a gene (e.g., mRNA, tRNA, rRNA, antisense RNA, ribozyme, shRNA, micro RNA, structural RNA or any other type of RNA) or a protein produced by translation of an mRNA. Gene products also include RNAs which are modified, by processes such as capping, polyadenylation, methylation, and editing, and proteins modified by, for example, methylation, acetylation, phosphorylation, ubiquitination, ADP-ribosylation, myristilation, and glycosylation. [0403] “Modulation” or “regulation” of gene expression refers to a change in the activity of a gene. Modulation of expression can include, but is not limited to, gene activation and gene repression. [0404] The term “operatively linked” or its equivalents (e.g., “linked operatively”) means two or more molecules are positioned with respect to each other such that they are capable of interacting to affect a function attributable to one or both molecules or a combination thereof. [0405] Non-covalently linked components and methods of making and using non-covalently linked components, are disclosed. The various components may take a variety of different forms as described herein. For example, non-covalently linked (i.e., operatively linked) proteins may be used to allow temporary interactions that avoid one or more problems in the art. The ability of non-covalently linked components, such as proteins, to associate and dissociate enables a functional association only or primarily under circumstances where such association is needed for the desired activity. The linkage may be of duration sufficient to allow the desired effect. [0406] A method for directing proteins to a specific locus in a genome of an organism is disclosed. The method may comprise the steps of providing a DNA localization component and providing an effector molecule, wherein the DNA localization component and the effector molecule are capable of operatively linking via a non-covalent linkage. [0407] A “target site” or “target sequence” is a nucleic acid sequence that defines a portion of a nucleic acid to which a binding molecule will bind, provided sufficient conditions for binding exist. [0408] The terms "nucleic acid" or "oligonucleotide" or "polynucleotide" refer to at least two nucleotides covalently linked together. The depiction of a single strand also defines the sequence of the complementary strand. Thus, a nucleic acid may also encompass the complementary strand of a depicted single strand. A nucleic acid of the disclosure also encompasses substantially identical nucleic acids and complements thereof that retain the same structure or encode for the same protein. [0409] Probes of the disclosure may comprise a single stranded nucleic acid that can hybridize to a target sequence under stringent hybridization conditions. Thus, nucleic acids of the disclosure may refer to a probe that hybridizes under stringent hybridization conditions. [0410] Nucleic acids of the disclosure may be single- or double-stranded. Nucleic acids of the disclosure may contain double-stranded sequences even when the majority of the molecule is single-stranded. Nucleic acids of the disclosure may contain single-stranded sequences even when the majority of the molecule is double-stranded. Nucleic acids of the disclosure may include genomic DNA, cDNA, RNA, or a hybrid thereof. Nucleic acids of the disclosure may contain combinations of deoxyribo- and ribo-nucleotides. Nucleic acids of the disclosure may contain combinations of bases including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine and isoguanine. Nucleic acids of the disclosure may be synthesized to comprise non-natural amino acid modifications. Nucleic acids of the disclosure may be obtained by chemical synthesis methods or by recombinant methods. [0411] Nucleic acids of the disclosure, either their entire sequence, or any portion thereof, may be non-naturally occurring. Nucleic acids of the disclosure may contain one or more mutations, substitutions, deletions, or insertions that do not naturally-occur, rendering the entire nucleic acid sequence non-naturally occurring. Nucleic acids of the disclosure may contain one or more duplicated, inverted or repeated sequences, the resultant sequence of which does not naturally-occur, rendering the entire nucleic acid sequence non-naturally occurring. Nucleic acids of the disclosure may contain modified, artificial, or synthetic nucleotides that do not naturally-occur, rendering the entire nucleic acid sequence non- naturally occurring. [0412] Given the redundancy in the genetic code, a plurality of nucleotide sequences may encode any particular protein. All such nucleotides sequences are contemplated herein. [0413] As used throughout the disclosure, the term "operably linked" refers to the expression of a gene that is under the control of a promoter with which it is spatially connected. A promoter can be positioned 5' (upstream) or 3' (downstream) of a gene under its control. The distance between a promoter and a gene can be approximately the same as the distance between that promoter and the gene it controls in the gene from which the promoter is derived. Variation in the distance between a promoter and a gene can be accommodated without loss of promoter function. [0414] As used throughout the disclosure, the term "promoter" refers to a synthetic or naturally-derived molecule which is capable of conferring, activating or enhancing expression of a nucleic acid in a cell. A promoter can comprise one or more specific transcriptional regulatory sequences to further enhance expression and/or to alter the spatial expression and/or temporal expression of same. A promoter can also comprise distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription. A promoter can be derived from sources including viral, bacterial, fungal, plants, insects, and animals. A promoter can regulate the expression of a gene component constitutively or differentially with respect to cell, the tissue or organ in which expression occurs or, with respect to the developmental stage at which expression occurs, or in response to external stimuli such as physiological stresses, pathogens, metal ions, or inducing agents. Representative examples of promoters include the bacteriophage T7 promoter, bacteriophage T3 promoter, SP6 promoter, lac operator-promoter, tac promoter, SV40 late promoter, SV40 early promoter, RSV-LTR promoter, CMV IE promoter, EF-1 Alpha promoter, CAG promoter, SV40 early promoter or SV40 late promoter and the CMV IE promoter. [0415] As used throughout the disclosure, the term “substantially complementary" refers to a first sequence that is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% identical to the complement of a second sequence over a region of 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 180, 270, 360, 450, 540, or more nucleotides or amino acids, or that the two sequences hybridize under stringent hybridization conditions. [0416] As used throughout the disclosure, the term "substantially identical" refers to a first and second sequence are at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98% or 99% identical over a region of 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 180, 270, 360, 450, 540 or more nucleotides or amino acids, or with respect to nucleic acids, if the first sequence is substantially complementary to the complement of the second sequence. [0417] As used throughout the disclosure, the term "variant" when used to describe a nucleic acid, refers to (i) a portion or fragment of a referenced nucleotide sequence; (ii) the complement of a referenced nucleotide sequence or portion thereof; (iii) a nucleic acid that is substantially identical to a referenced nucleic acid or the complement thereof; or (iv) a nucleic acid that hybridizes under stringent conditions to the referenced nucleic acid, complement thereof, or a sequences substantially identical thereto. [0418] As used throughout the disclosure, the term "vector" refers to a nucleic acid sequence containing an origin of replication. A vector can be a viral vector, bacteriophage, bacterial artificial chromosome or yeast artificial chromosome. A vector can be a DNA or RNA vector. A vector can be a self-replicating extrachromosomal vector, and preferably, is a DNA plasmid. A vector may comprise a combination of an amino acid with a DNA sequence, an RNA sequence, or both a DNA and an RNA sequence. [0419] As used throughout the disclosure, the term "variant" when used to describe a peptide or polypeptide, refers to a peptide or polypeptide that differs in amino acid sequence by the insertion, deletion, or conservative substitution of amino acids, but retain at least one biological activity. Variant can also mean a protein with an amino acid sequence that is substantially identical to a referenced protein with an amino acid sequence that retains at least one biological activity. [0420] A conservative substitution of an amino acid, i.e., replacing an amino acid with a different amino acid of similar properties (e.g., hydrophilicity, degree and distribution of charged regions) is recognized in the art as typically involving a minor change. These minor changes can be identified, in part, by considering the hydropathic index of amino acids, as understood in the art. Kyte et al., J. Mol. Biol.157: 105-132 (1982). The hydropathic index of an amino acid is based on a consideration of its hydrophobicity and charge. Amino acids of similar hydropathic indexes can be substituted and still retain protein function. In an aspect, amino acids having hydropathic indexes of ±2 are substituted. The hydrophilicity of amino acids can also be used to reveal substitutions that would result in proteins retaining biological function. A consideration of the hydrophilicity of amino acids in the context of a peptide permits calculation of the greatest local average hydrophilicity of that peptide, a useful measure that has been reported to correlate well with antigenicity and immunogenicity. U.S. Patent No.4,554,101, incorporated fully herein by reference. [0421] Substitution of amino acids having similar hydrophilicity values can result in peptides retaining biological activity, for example immunogenicity. Substitutions can be performed with amino acids having hydrophilicity values within ±2 of each other. Both the hydrophobicity index and the hydrophilicity value of amino acids are influenced by the particular side chain of that amino acid. Consistent with that observation, amino acid substitutions that are compatible with biological function are understood to depend on the relative similarity of the amino acids, and particularly the side chains of those amino acids, as revealed by the hydrophobicity, hydrophilicity, charge, size, and other properties. [0422] As used herein, “conservative” amino acid substitutions may be defined as set out in Tables A, B, or C below. In some aspects, fusion polypeptides and/or nucleic acids encoding such fusion polypeptides include conservative substitutions have been introduced by modification of polynucleotides encoding polypeptides of the disclosure. Amino acids can be classified according to physical properties and contribution to secondary and tertiary protein structure. A conservative substitution is a substitution of one amino acid for another amino acid that has similar properties. Exemplary conservative substitutions are set out in Table 1C. Table 1C – Conservative Substitutions I [0423] Alternately, conservative amino acids can be grouped as described in Lehninger, (Biochemistry, Second Edition; Worth Publishers, Inc. NY, N.Y. (1975), pp.71-77) as set forth in Table 2. Table 2 – Conservative Substitutions II [0424] Alternately, exemplary conservative substitutions are set out in Table 3. Table 3 – Conservative Substitutions III [0425] It should be understood that the polypeptides of the disclosure are intended to include polypeptides bearing one or more insertions, deletions, or substitutions, or any combination thereof, of amino acid residues as well as modifications other than insertions, deletions, or substitutions of amino acid residues. Polypeptides or nucleic acids of the disclosure may contain one or more conservative substitution. [0426] As used throughout the disclosure, the term “more than one” of the aforementioned amino acid substitutions refers to 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 or more of the recited amino acid substitutions. The term “more than one” may refer to 2, 3, 4, or 5 of the recited amino acid substitutions. [0427] Polypeptides and proteins of the disclosure, either their entire sequence, or any portion thereof, may be non-naturally occurring. Polypeptides and proteins of the disclosure may contain one or more mutations, substitutions, deletions, or insertions that do not naturally-occur, rendering the entire amino acid sequence non-naturally occurring. Polypeptides and proteins of the disclosure may contain one or more duplicated, inverted or repeated sequences, the resultant sequence of which does not naturally-occur, rendering the entire amino acid sequence non-naturally occurring. Polypeptides and proteins of the disclosure may contain modified, artificial, or synthetic amino acids that do not naturally- occur, rendering the entire amino acid sequence non-naturally occurring. [0428] As used throughout the disclosure, “sequence identity” may be determined by using the stand-alone executable BLAST engine program for blasting two sequences (bl2seq), which can be retrieved from the National Center for Biotechnology Information (NCBI) ftp site, using the default parameters (Tatusova and Madden, FEMS Microbiol Lett., 1999, 174, 247-250; which is incorporated herein by reference in its entirety). The terms "identical" or "identity" when used in the context of two or more nucleic acids or polypeptide sequences, refer to a specified percentage of residues that are the same over a specified region of each of the sequences. The percentage can be calculated by optimally aligning the two sequences, comparing the two sequences over the specified region, determining the number of positions at which the identical residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the specified region, and multiplying the result by 100 to yield the percentage of sequence identity. In cases where the two sequences are of different lengths or the alignment produces one or more staggered ends and the specified region of comparison includes only a single sequence, the residues of single sequence are included in the denominator but not the numerator of the calculation. When comparing DNA and RNA, thymine (T) and uracil (U) can be considered equivalent. Identity can be performed manually or by using a computer sequence algorithm such as BLAST or BLAST 2.0. [0429] As used throughout the disclosure, the term "endogenous" refers to nucleic acid or protein sequence naturally associated with a target gene or a host cell into which it is introduced. [0430] As used throughout the disclosure, the term "exogenous" refers to nucleic acid or protein sequence not naturally associated with a target gene or a host cell into which it is introduced, including non-naturally occurring multiple copies of a naturally occurring nucleic acid, e.g., DNA sequence, or naturally occurring nucleic acid sequence located in a non- naturally occurring genome location. [0431] The disclosure provides methods of introducing a polynucleotide construct comprising a DNA sequence into a host cell. By "introducing" is intended presenting to the cell the polynucleotide construct in such a manner that the construct gains access to the interior of the host cell. The methods of the disclosure do not depend on a particular method for introducing a polynucleotide construct into a host cell, only that the polynucleotide construct gains access to the interior of one cell of the host. Methods for introducing polynucleotide constructs into bacteria, plants, fungi and animals are known in the art including, but not limited to, stable transformation methods, transient transformation methods, and virus-mediated methods. EXAMPLES [0432] For the following Examples, Compound Numbers are assigned to compounds of Formula (I) and (II) of the present disclosure according to the following: Example 1— Preparation of COMPOUND NO.1 [0433] COMPOUND NO.1 was prepared in accordance with the General Scheme (A). The crude was purified by silica gel flash column chromatography. ¹H NMR (500 MHz, CDCl3) δ 7.26 (br, 1H), 7.13 (br, 1H), 4.01 – 3.84 (m, 4H), 3.32-3.25 (m, 6H), 3.13-3.05 (m, 6H), 2.94-2.93 (m,4H), 2.74-2.69 (m, 4H), 2.37-2.34 (m, 4H), 2.05-1.99 (m, 4H), 1.82-1.80 (m, 4H), 1.62-1.37 (m, 20H), 1.34-1.20 (m, 62H), 0.88 (t, J=10Hz, 12H). MS (ESI): calcd. for C64H130N4O6S2 [M+H]⁺ 1114.9, found 1116.3. Example 2— Preparation of COMPOUND NO.2 [0434] COMPOUND NO.2 was prepared in accordance with the General Scheme (A). The crude was purified by silica gel flash column chromatography. ¹H NMR (500 MHz, CDCl3) δ 4.11 – 4.09 (m, 4H), 3.62-3.60 (m, 4H),2.62(s, 4H), 2.59-2.53 (m,6H), 2.42-2.37 (m, 6H), 1.63-1.53 (m, 6H), 1.51-1.45 (m, 6H), 1.44-1.40 (m, 4H), 1.39-1.36 (m, 8H), 1.33-1.25 (m, 68H), 0.88 (t, J=10Hz, 12H). MS (ESI): calcd. for C64H128N2O8S2 [M+H]⁺ 1116.9, found 1118.2. Example 3— Preparation of COMPOUND NO.3 [0435] COMPOUND NO.3 was prepared in accordance with the General Scheme (A). The crude was purified by silica gel flash column chromatography. ¹H NMR (500 MHz, CDCl3) δ 4.09 – 4.07 (m, 4H), 3.62-3.60 (m, 4H),2.73-2.70(t, J=10Hz, 4H), 2.59-2.53 (m, 4H), 2.45- 2.38 (m, 10H), 2.04-2.0 (m, 4H), 1.65-1.40 (m, 14H), 1.33-1.25 (m, 64H), 0.88 (t, J=10Hz, 12H). MS (ESI): calcd. for C₆₀H₁₂₀N₂O₈ [M+H]⁺ 996.9, found 998.1. Example 4— Preparation of COMPOUND NO.4 [0436] COMPOUND NO.4 was prepared in accordance with the General Scheme (A). ¹H NMR (500 MHz, CDCl3) δ 6.5 (br, 2H), 4.05 – 4.02 (m, 4H), 3.72-3.39 (m, 16H),3.28-3.25 (m, 4H), 2.96-2.85 (m, 16H), 2.72-2.65 (m, 8H), 2.33-2.31 (m, 4H), 2.05-2.01(m,4H), 1.69- 1.50 (m, 30H), 1.35-1.10 (m, 34H)-0.82-0.91(m, 8H). MS (ESI): calcd. for C68H130N4O10S2 [M+H]⁺ 1227.9, found 1228.6. Example 5— Preparation of COMPOUND NO.5 [0437] COMPOUND NO.5 was prepared in accordance with the General Scheme (A). ¹H NMR (500 MHz, CDCl3) δ 6.5 (br, 2H), 3.98 (m, 4H), 3.40-3.38 (m, 8H) 3.27-3.24 (m, 12H),2.84-2.66 (m, 20H), 2.38-2.30 (m, 20H), 2.38-2.30 (m, 4H), 2.03-1.48 (m, 16H), 1.25- 1.15(m,45H), 0.89-0.85 (m, 39H). MS (ESI): calcd. for C₈₈H₁₇₀N₄O₁₀S₂ [M+H]⁺ 1508.2, found 1508.9. Example 6— Preparation of COMPOUND NO.6 [0438] COMPOUND NO.6 was prepared in accordance with the General Scheme (A). MS (ESI): calcd. for C72H146N4O6S2 [M+H]⁺ 1228.1, found 1227.8. Example 7— Preparation of COMPOUND NO.7 [0439] COMPOUND NO.7 was prepared in accordance with the General Scheme (A). ¹H NMR (500 MHz, CDCl3) δ 7.01-7.1 (br, 2H), 4.28 (s, 4H), 4.03-3.97 (m, 4H) 3.72-3.64 (m, 4H),3.27 (br, 6H), 3.13-2.97(m, 8H), 2.71-2.65 (m, 4H), 2.50-2.49 (m, 4H), 1.59-1.57 (m,6H), 1.447-1.36 (m, 16H), 1.31-1.25 (m, 64H), 0.89-0.85 (m, 12H). MS (ESI): calcd. for C66H130N4O10 [M+H]⁺ 1140.1, found 1140.6. Example 8— Preparation of COMPOUND NO.8 [0440] COMPOUND NO.8 was prepared in accordance with the General Scheme (B). ¹H NMR (500 MHz, DMSO): δ 7.7 (br, 1H), 4.27-4.21 (br, 4H), 4.43 (m, 4H), 3.17 (m, 2H), 2.49-2.02(m, 8H), 1.37-1.24 (m, 84H), 0.85(m, 12H). MS (ESI): calcd. for C57H117N3O5 [M+H]⁺ 924.9, found 926.2. Example 9— Preparation of COMPOUND NO.9 [0441] COMPOUND NO.9 was prepared in accordance with the General Scheme (B). MS (ESI): calcd. for C41H85N3O5 [M+H]⁺ 700.6, found 701.3. Example 10— Preparation of COMPOUND NO.10 [0442] COMPOUND NO.10 was prepared in accordance with the General Scheme (B). MS (ESI): calcd. for C65H133N3O5 [M+H]⁺ 1037, found 1037.6. Example 11— Preparation of COMPOUND NO.11 [0443] COMPOUND NO.11 was prepared in accordance with the General Scheme (B). MS (ESI): calcd. for C73H149N3O5 [M+H]⁺ 1149.1, found 1149.7. Example 12— Preparation of COMPOUND NO.12 [0444] COMPOUND NO.12 was prepared in accordance with the General Scheme (B). MS (ESI): calcd. for C69H141N3O9 [M+H]⁺ 1157.1, found 1157.5. Example 13— Preparation of COMPOUND NO.13 [0445] COMPOUND NO.13 was prepared in accordance with the General Scheme (B). MS (ESI): calcd. for C₅₃H₁₀₉N₃O₉ [M+H]⁺ 932.8, found 933.2. Example 14— Preparation of COMPOUND NO.14 [0446] COMPOUND NO.14 was prepared in accordance with the General Scheme (B). MS (ESI): calcd. for C₆₁H₁₁₇N₃O₉ [M+H]⁺ 1036.9, found 1037.2. Example 15— Preparation of COMPOUND NO.15 [0447] COMPOUND NO.15 was prepared in accordance with the General Scheme (B). MS (ESI): calcd. for C₇₄H₁₄₆N₄O₁₀ [M+H]⁺ 1252.1, found 1252.6. Example 16— Preparation of COMPOUND NO.16 [0448] COMPOUND NO.16 was prepared in accordance with the General Scheme (C). MS (ESI): calcd. for C₉₀H₁₈₄N₆O₈ [M+H]⁺ 1478.4, found 1479.1. Example 17— Preparation of COMPOUND NO.17 [0449] COMPOUND NO.17 was prepared in accordance with the General Scheme (C). MS (ESI): calcd. for C₁₀₀H₁₉₆N₆O₁₅ [M+H]⁺ 1722.5, found 1723.3. Example 18— Preparation of COMPOUND NO.18 [0450] COMPOUND NO.18 was prepared in accordance with the General Scheme (C). MS (ESI): calcd. for C₁₁₂H₂₂₀N₆O₁₅ [M+H]⁺ 1890.7, found 1890.4. Example 19— Preparation of COMPOUND NO.19 [0451] COMPOUND NO.19 was prepared in accordance with the General Scheme (C). ¹H NMR (500 MHz, CDCl3) δ 4.67 (m, 2H), 4.26-3.81 (m, 12H), 3.27-3.02 (m, 12H), 2.55 (s, 8H), 2.22-2.15 (m, 4H), 2.05-1.97(m, 4H), 1.79-1.55(m, 8H), 1.71-1.17 (m, 72H), 0.89-0.85 (m, 12H). MS (ESI): calcd. for C72H136N4O14 [M+H]⁺ 1282.2, found 1282.1. Example 20— Preparation of COMPOUND NO.20 [0452] COMPOUND NO.20 was prepared in accordance with the General Scheme (D). MS (ESI): calcd. for C77H141N3O17 [M+H]⁺ 1381, found 1381.5. Example 21— Preparation of COMPOUND NO.21 [0453] COMPOUND NO.21 was prepared in accordance with the General Scheme (E). ¹H NMR (500 MHz, CDCl3) δ 4.44 (t, J=10 Hz, 1H), 3.64-3.42 (m, 8H), 2.91-2.74 (m, 12H), 1.59-1.26 (m, 100H), 0.89 (t, J=5Hz, 15H). MS (ESI): calcd. for C66H136N2O6 [M+H]⁺ 1054, found 1054.2. Example 22— Preparation of COMPOUND NO.22 [0454] COMPOUND NO.22 was prepared in accordance with the General Scheme (E). ¹H NMR (500 MHz, CDCl3) δ 5.12 (br, 1H), 4.08-4.07 (m, 2H), 3.65-3.68 (m, 4H), 2.72- 2.45(m, 12H), 1.75-1.26 (m, 80H), 0.86 (t, J=5 Hz, 12H). MS (ESI): calcd. for C₅₇H₁₁₇N₃O₆ [M+H]⁺ 940.9, found 941.1. Example 23 - Preparation of LNPs of Present Disclosure Comprising mRNA or DNA and In Vivo Screening [0455] The following is a nonlimiting example that provides exemplary methods for formulating a plurality of multi-component LNP compositions comprising exemplary compounds of Formula (I), Formula (II’), or Formula (II) and mRNA or DNA. [0456] To formulate the LNPs, COMPOUND NO.8, the phospholipid DOPC, the structural lipid cholesterol (Chol) and 1,2-dimyristoyl-sn-glycerol methoxypolyethylene glycol (DMG- PEG2000; Avanti Polar Lipids, Alabaster, Alabama, USA) were combined to prepare LNP compositions. [0457] Individual 25 mg/ml stock solutions were prepared by solubilizing the lipids in 200- proof HPLC-grade ethanol and stock solutions were stored at -80° C until formulated. At the time of formulation, the lipid stock solutions were briefly allowed to equilibrate to room temp and then placed on a hot plate maintained at a temperature range of 50-55^oC. Subsequently, the hot lipid stock solutions were combined to yield desired final mol percentages. [0458] A 1 mg/ml solution of the desired nucleic acid to be incorporated into the LNPs was added to 150 mM sodium acetate buffer (pH 5.2) to form a stock solution and kept on ice. The ethanol phase was vigorously mixed with the nucleic acid in sodium acetate phase using the Precision Nanoassemblr instrument. [0459] The resultant LNP compositions were then transferred to a Repligen Float-A-Lyzer dialysis device- having a molecular weight cut off (MWCO) of 8-10kDa (Spectrum Chemical Mfg. Corp, CA, USA) and processed by dialysis against phosphate buffered saline (PBS) (dialysate : dialysis buffer volume at least 1:200 v/v), pH 7.4 overnight at 4°C (or alternatively room temperature for at least 4 hours), to remove the 25% ethanol and achieve a complete buffer exchange. In some experiments the LNPs were further concentrated by in an Amicon® Ultra-4 centrifugal filter unit, MWCO-30kDa (Millipore Sigma, USA) spun at ~4100 x g in an ultracentrifuge. The LNPs were then stored at 4°C until further use. [0460] In one experiment, LNP compositions of the present disclosure comprising COMPOUND NO.8 and RNA encoding firefly luciferase (TriLink BioTechnologies) were prepared as described above. The LNP compositions are shown in Table 4. Table 4 [0461] Adult female BALB/C mice (n=3/group) were intravenously administered 0.5-0.7 mg/kg of 5’-CleanCap--fLuciferase mRNA (TriLink Biotech) formulated with the LNP compositions shown in Table 4. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. [0462] In another experiment, LNP compositions of the present disclosure comprising COMPOUND NO.8 and DNA encoding firefly luciferase (Nature Technology Corporation) were prepared as described above. The LNP compositions are shown in Table 5. Table 5 [0463] The location and extent of luciferase expression in treated and control mice were determined at 4 hr for mRNA and 48 hr for DNA by bioluminescent imaging (BLI) of anesthetized mice using an IVIS Lumina in vivo imaging system (Perkin Elmer) according to the manufacturer’s instructions. Briefly, mice were anesthetized using isoflurane in oxygen, and placed supine on a heated stage. Mice were then administered D-luciferin (Perkin-Elmer #122799) IP, and BLI was performed. The results for mRNA are shown in Table 6 and DNA are shown in Table 7. Table 6 Table 7 [0464] Visual analysis of the BLI images revealed that the BLI signal was predominantly located in the liver. Accordingly, as shown in Table 6 and Table 7, LNP compositions of the present disclosure successfully delivered mRNA or DNA in vivo to liver cells and the encoded transgene was expressed in the liver cells. Example 24 - Preparation of LNPs of Present Disclosure Comprising mRNA and In Vivo Screening [0465] The following is a nonlimiting example that provides exemplary methods for formulating a plurality of multi-component LNP compositions comprising exemplary compounds of Formula (I) , Formula (II’), or Formula (II) and mRNA. [0466] LNP compositions of the present disclosure comprising one of COMPOUND NOS.1- 14 and RNA encoding firefly luciferase (TriLink BioTechnologies) were prepared as described in Example 23. The LNP compositions are shown in Table 8. Table 8 [0467] Adult female BALB/C mice (n=3/group) were intravenously administered 0.5 mg/kg of 5’-CleanCap--fLuciferase mRNA (TriLink Biotech) formulated with the LNP compositions shown in Table 8. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. [0468] The location and extent of luciferase expression in treated and control mice were determined at 4 hr by bioluminescent imaging (BLI) of anesthetized mice using an IVIS Lumina in vivo imaging system (Perkin Elmer) according to the manufacturer’s instructions. Briefly, mice were anesthetized using isoflurane in oxygen, and placed supine on a heated stage. Mice were then administered D-luciferin (Perkin-Elmer #122799) IP, and BLI was performed. The results are shown in Table 9. Table 9 [0469] As shown in this Example, LNP compositions of the present disclosure successfully delivered mRNA in vivo, as shown by visual BLI analysis predominantly to cells in the liver, and the encoded transgene was subsequently expressed by the cells. Example 25 - Preparation of LNPs of Present Disclosure Comprising mRNA and In Vivo Screening [0470] LNP compositions of the present disclosure comprising COMPOUND NO.1 and RNA encoding firefly luciferase (TriLink BioTechnologies) were prepared as described in Example 23. The LNP compositions are shown in Table 10. Table 10 [0471] Mice were treated with the LNP compositions and BLI was performed as described in Example 23. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. The results are shown in Table 11. Table 11 [0472] As shown in this Example, LNP compositions of the present disclosure successfully delivered mRNA in vivo, as shown by visual BLI analysis predominantly to cells in the liver, and the encoded transgene was subsequently expressed by the cells. Example 26 - Preparation of LNPs of Present Disclosure Comprising mRNA and In Vivo Screening [0473] LNP compositions of the present disclosure comprising one of COMPOUND NOs.1- 14 and RNA encoding firefly luciferase (TriLink BioTechnologies) were prepared as described in Example 23. The LNP compositions are shown in Table 12. Table 12 [0474] Mice were treated with the LNP compositions and BLI was performed as described in Example 23. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. The results are shown in Table 13. Table 13 [0475] As shown in this Example, LNP compositions of the present disclosure successfully delivered mRNA in vivo, as shown by visual BLI analysis predominantly to cells in the liver, and the encoded transgene was subsequently expressed by the cells. Example 27 - Preparation of LNPs of Present Disclosure Comprising mRNA and In Vivo Screening [0476] LNP compositions of the present disclosure comprising one of COMPOUND NOs.1- 14 and RNA encoding firefly luciferase (TriLink BioTechnologies) were prepared as described in Example 23. The LNP compositions are shown in Table 14. Table 14 [0477] Mice were treated with the LNP compositions and BLI was performed as described in Example 23. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. The results are shown in Table 15. Table 15 [0478] As shown in this Example, LNP compositions of the present disclosure successfully delivered mRNA in vivo, as shown by visual BLI analysis predominantly to cells in the liver, and the encoded transgene was subsequently expressed by the cells. Example 28 - LNP compositions of present disclosure deliver RNA with high specificity to the liver in vivo [0479] This example shows the ability of LNP compositions of the present disclosure to deliver Cas-CLOVER mRNA to the liver, targeted by a pair of gRNAs to the psk9 gene, resulting in subsequent in vivo gene editing of the psk9 gene. As would be appreciated by the skilled artisan, Pcsk9 protein is secreted by hepatocytes and binds to the LDL receptor, inducing its internalization and lysosomal degradation, resulting in increased circulating levels of LDL-cholesterol. [0480] In two separate experiments, each group of adult female BALB/C mice (n=2/group) was intravenously co-administered mRNA encoding 5’-CleanCap-5MeC-Cas-CLOVER (SEQ ID NO: 7) and a pair of gRNAs (SEQ ID NOs: 8 and 9) targeted to the first exon of the mouse pcsk9 gene. [0481] In the first experiment, the mRNA and gRNA molecules were formulated within LNP compositions of the present disclosure comprising COMPOUND NO.8 as shown in Table 16. All uridine residues in the mRNA were N1-methylpseudouridine. Table 16 [0482] Mice from each group were administered a dose (0.5 mg/kg) of Cas-CLOVER mRNA and a pair of pcsk9 gRNA, both co-encapsulated in an LNP composition of the present disclosure. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. Another group of mice was treated with a benchmark LNP composition comprising the cationic lipid ssPalmO-Ph-P4C2: , as described in Akita et al., (2020) Biol. Phar. Bull.43:1617 – 1625. [0483] In the second experiment, the mRNA and gRNA molecules were formulated within LNP compositions of the present disclosure comprising COMPOUND NO.1 as shown in Table 17. All uridine residues in the mRNA were N1-methylpseudouridine. Table 17 [0484] Mice from each group were administered a dose (0.5 mg/kg) of Cas-CLOVER mRNA and a pair of pcsk9 gRNA, both co-encapsulated in an LNP composition of the present disclosure. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. [0485] After seven days post-administration, blood samples were drawn from the subjects. Briefly, 500uL of blood was collected after euthanasia via cardiac puncture using 2ml syringes and 25G needles, transferred to microcentrifuge tubes, incubated at room temperature for 1 hour, and centrifuged at 1500g for 15 minutes to separate the cellular fraction from serum. Serum fraction (200uL) was transferred to a new tube and stored at -80C until further analysis. [0486] Serum levels of the pcsk9 protein in the mice were measured 7 days after administration. Results are shown in Table 18 for the first experiment and Table 19 for the second experiment. Briefly, a mouse Pcsk9 ELISA kit (Biolegend) was used to determine Pcsk9 in each serum sample following manufacturer’s instructions. All serum samples were assayed in triplicate and results were expressed as percentage in Pcsk9 levels compared with Pcsk9 levels of PBS-treated mice. Table 18 Table 19 [0487] The results of these experiments show that Cas-CLOVER mRNA delivered by LNP compositions of the present disclosure is effective at editing the pcsk9 gene in the liver in vivo. Additionally, Cas-CLOVER mRNA delivered by certain LNP compositions of the present disclosure was much more effective at editing the pcsk9 gene in the liver in vivo compared to a benchmark LNP composition. Example 29- In vivo LNP delivery of co-encapsulated mRNA and DNA to liver [0488] The following is a nonlimiting example that provides exemplary methods for formulating a plurality of multi-component LNP compositions comprising exemplary compounds of Formula (I) and co-encapsulated mRNA and DNA. [0489] In these experiments, luciferase expression indicates successful delivery by LNP compositions of a two-component, DNA/RNA system to liver cells, resulting in transposition of the luciferase transgene facilitated by SPB. [0490] Adult BALB/C mice (n=3) were administered a single co-encapsulated LNP encapsulating both firefly luciferase transposon and SPB. The compositions of the co- encapsulated LNPs are shown in Table 20 and were prepared as described in Example 23, incorporating mRNA encoding active SPB and nanoplasmid DNA comprising the transposon (SEQ ID NO: 10). All cytidine residues in the mRNA were 5-methylcytidine (5-MeC). Table 20 [0491] Mice received either 0.5 mg/kg or 1.0 mg/kg of co-encapsulated LNP encapsulating mRNA and DNA at 1:2 mRNA:DNA ratio. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. [0492] The location and extent of luciferase expression in treated and control mice were determined as described in Example 15 and the results are shown in Table 21. Table 21 [0493] This example shows that LNP compositions of the present disclosure successfully delivered a two-component, DNA/RNA system to liver cells as shown by visual BLI analysis, and the desired transgene was stably integrated into the genome and not episomal. Example 30- In vivo LNP delivery of co-encapsulated mRNA and DNA to liver with improved tolerability [0494] The following is a non-limiting example demonstrating that lipid nanoparticle compositions of the present disclosure comprising GalNac can be used to deliver co- encapsulated mRNA and DNA to liver cells in vivo with improved tolerability compared to a benchmark LNP composition comprising GalNac or LNP compositions of the present disclosure that did not comprise GalNac. [0495] As described in Example 29, luciferase expression in this Example indicates successful delivery by LNP compositions of a two-component, DNA/RNA system to liver cells, resulting in transposition of the luciferase transgene facilitated by SPB. [0496] Adult BALB/C mice (n=3) were administered a single co-encapsulated LNP encapsulating both firefly luciferase transposon and SPB. The compositions of the co- encapsulated LNPs are shown in Table 22 and were prepared as described in Example 23, incorporating mRNA encoding active SPB and nanoplasmid DNA comprising the transposon (SEQ ID NO: 10). All cytidine residues in the mRNA were 5-methylcytidine (5-MeC). Table 22 [0497] Mice received 1.0 mg/kg of co-encapsulated LNP encapsulating mRNA and DNA at 1:2 mRNA:DNA ratio. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. Another group of mice was treated with a benchmark LNP composition comprising the cationic lipid HMA-404 with the following structure: , prepared as described in PCT Application No. PCT/US2023/061005. [0498] The location and extent of luciferase expression in treated and control mice were determined as described in Example 23 and the results are shown in Table 23. LNP compositions of the present disclosure successfully delivered a two-component, DNA/RNA system to liver cells, as indicated by the luciferase expression levels compared to vehicle as shown in Table 23. Table 23 [0499] The levels of five proinflammatory cytokines present in serum were evaluated at 4 hours after LNP administration for each of the tested concentrations. Briefly, serum samples were prepared as described for liver enzyme analysis and the serum concentration of each cytokine was determined using commercially available ELISA kits (e.g., R&D Systems Quantikine ELISA kits). The levels of the proinflammatory cytokines interleukin-6 (IL-6), interferon gamma (INF-G), tumor necrosis factor alpha (TNF-a), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 beta (MIP-1b) in mice treated with LNPs of the present disclosure compared to vehicle treated mice at 4 hours are shown in Table 24. Table 24: Cytokine concentration (pg/ml) [0500] The results of this example show that the addition of GalNac to LNP compositions of the present disclosure for the administration of co-encapsulated mRNA and DNA to liver cells in vivo improved tolerability, including compared to LNP compositions of the present disclosure that did not comprise GalNac. LNP compositions of the present disclosure with GalNac (e.g., LNP IDs A.3, A.9, A.10, A.11, A.12) exhibited comparable or higher luciferase expression and comparable, or even reduced, cytokine induction. Further, the addition of GalNac to certain LNP compositions of the present disclosure resulted in significantly lower cytokine levels compared to the same LNP compositions without GalNac (e.g., compare LNP ID. A.3 and A.9 to LNP ID. A.13; LNP ID. A.6 to LNP ID A.2; LNP ID A.11 and A.12 to LNP ID A.1; LNP ID A.8 to LNP ID A.7; LNP ID A.10 to LNP ID A.1). Example 31 – In vivo LNP delivery of co-encapsulated mRNA and DNA to liver [0501] In this experiment, FVIII expression indicates successful delivery by LNP compositions of a two-component, DNA/RNA system to liver cells, resulting in transposition of the FVIII transgene facilitated by SPB. [0502] Wild-type C57BL/6 adult mice (N=4) were dosed with a single co-encapsulated LNP encapsulating both FVIII transposon and SPB. The compositions of the co-encapsulated LNPs are shown in Table 25, incorporating mRNA encoding active SPB and TTR-FVIII nanoplasmid DNA (SEQ ID NO: 9). All cytidine residues in the mRNA were 5- methylcytidine (5-MeC). Table 25 [0503] Each group of mice received 0.75 mg/kg or 1mg/kg of co-encapsulated LNP encapsulating mRNA and DNA at a 1:2 mRNA:DNA ratio. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. [0504] Prior to administration, mice were placed under anesthesia induced by isoflurane. For delivery, 50-80µL of co-encapsulated LNP was drawn into a single 29 gauge insulin syringe, and delivered via intravenous (IV) through the retro-orbital sinus. On Day 6 post-treatment, plasma was collected from treated mice. For plasma collection, treated mice were put under anesthesia with isoflurane, approximately 150µL whole blood was retro-orbitally collected, whole blood was mixed with 10% volume of 3.2% sodium citrate, centrifuged at 15,000g for 15 minutes at 20°C, and plasma supernatant was collected. hFVIII antigen levels were measured using the Visualize^TM Factor VIII Antigen Plus Kit (Affinity Biologicals^TM Inc.). [0505] The results of FVIII antigen expression are shown in Table 26. Table 26 [0506] As shown in Table 26, LNP compositions comprising Compound NO.1 resulted in an increase in FVIII antigen expression of up to about 41% compared to vehicle. Example 32- Preparation of LNPs of Present Disclosure Comprising DNA and In Vivo Screening [0507] The following is a nonlimiting example that provides exemplary methods for formulating a plurality of multi-component LNP compositions comprising exemplary compounds of Formula (I) and DNA. [0508] LNP compositions of the present disclosure comprising COMPOUND NO.1 and DNA encoding firefly luciferase (Nature Technology Corporation) were prepared as described in Example 23. The LNP compositions are shown in Table 27. Table 27 [0509] The location and extent of luciferase expression in treated and control mice were determined at 48 hr for DNA by bioluminescent imaging (BLI) of anesthetized mice using an IVIS Lumina in vivo imaging system (Perkin Elmer) according to the manufacturer’s instructions. Briefly, mice were anesthetized using isoflurane in oxygen, and placed supine on a heated stage. Mice were then administered D-luciferin (Perkin-Elmer #122799) IP, and BLI was performed. The results are shown in Table 28. Table 28 [0510] The results of this example show that LNP compositions of the present disclosure successfully delivered DNA in vivo, as shown by visual BLI analysis predominantly to cells in the liver, and the encoded protein was subsequently expressed by the cells. Example 33 - LNP compositions comprising tannic acid enhance delivery of DNA to liver cells in vivo [0511] This experiment shows the ability of LNP compositions of the present disclosure that comprise tannic acid to enhance delivery of DNA to liver cells in vivo. [0512] In this experiment, each group of adult female BALB/C mice (n=3/group) was intravenously administered via tail vein injection a DNA nanoplasmid encoding the fluc gene operably associated with the constitutive CMV promoter. The DNA molecules were formulated within LNP compositions shown in Table 29 and the LNP compositions of the present disclosure (0.5 mg/kg) were administered to the mice from each group. Table 29 [0513] The results of BLI measurements (total flux [p/s]) are shown in Table 30. Table 30 [0514] As shown in Table 30, the addition of tannic acid to the LNP composition resulted in an increase in BLI of up to 84-fold compared to LNP composition lacking tannic acid (C.1). Example 34 - Preparation of LNPs of Present Disclosure Comprising mRNA or DNA and In Vivo Screening [0515] LNP compositions of the present disclosure comprising one of COMPOUND NOs.1- 22 and RNA encoding firefly luciferase (TriLink BioTechnologies) or DNA encoding firefly luciferase (Nature Technology Corporation) were prepared as described in Example 23. The LNP compositions are shown in Table 31. Table 31 [0516] Mice were treated with the LNP compositions and BLI was performed as described in Example 23. One group of mice was treated with vehicle (PBS, Thermo Fisher Scientific, USA) as a negative control. The results for RNA delivery are shown in Table 32 and the results for DNA delivery are shown in Table 33. Table 32 Table 33 As shown in this Example, LNP compositions of the present disclosure successfully delivered mRNA or DNA in vivo, as shown by visual BLI analysis predominantly to cells in the liver, and the encoded transgene was subsequently expressed by the cells. [0517] While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth, and as follows in the scope of the appended claims.

Claims

What is claimed is: 1. A compound of Formula (I): Formula (I) or a salt thereof, wherein: covalent bond; each of Xa, Xb and Xc is independently NH or O; each of Ya, Yb, Yc, Yd, Ye and Yf is independently C or O; each of r, s and t is independently an integer ranging from 1 to 9; and each of R2a, R2b, R2c, R2d, R2e, and R2f is independently C1-C18 alkyl, C2-C18 alkenyl, - (cyclohexyl)-(C1-C18 alkyl), -(cyclohexyl)-(C2-C18 alkenyl), or -(cyclohexyl)-(CH2-O-CO)- (C₁-C₁₈ alkyl), wherein the C₁-C₁₈ alkyl or C₂-C₁₈ alkenyl is optionally substituted with one or more cyclohexyl. 2. The compound of claim 1, wherein Z is . 3. The compound of claim 1, wherein Z is .

4. The compound of any one of claims 1-3, wherein each of Xa, Xb and Xc is NH. 5. The compound of any one of claims 1-3, wherein each of Xa, Xb and Xc is O. 6. The compound of any one of claims 1-5, wherein each of Y_a, Y_b, Y_c, Y_d, Y_e and Y_f is C. 7. The compound of any one of claims 1-5, wherein each of Ya, Yb, Yc, Yd, Ye and Yf is O. 8. The compound of any one of claims 1-7, wherein each of R_2a, R_2b, R_2c, R_2d, R_2e, and R_2f is C1-C18 alkyl. 9. The compound of any one of claims 1-8, wherein each of R_2a, R_2b, R_2c, and R_2d is C₁-C₁₈ alkyl substituted with one or more cyclohexyl. 10. The compound of any one of claims 1-9, wherein each of R_2a, R_2b, R_2c, and R_2d is . 12. The compound of claim 1, wherein Z is and each of Xa and Xb is NH. 13. The compound of claim 1, wherein Z is and each of Xa and Xb is O. 14. The compound of claim 1, wherein Z is a covalent bond and each of Xa and Xb is O.

15. The compound of claim 1, wherein Z is and each of Xa and Xb is NH. 16. The compound of any one of claims 12-15, wherein each of Ya, Yb, Yc and Yd is C. 17. The compound of any one of claims 12-15, wherein each of Y_a, Y_b, Y_c and Y_d is O. 18. The compound of any one of claims 12-17, wherein each of R_2a, R_2b, R_2c, and R_2d is C₃- C₁₈ alkyl. 19. The compound of any one of claims 12-18, wherein each of R2a, R2b, R2c, and R2d is C3- C₁₈ alkyl substituted with one or more cyclohexyl. 20. The compound of any one of claims 12-19, wherein each of R2a, R2b, R2c, and R2d is . 22. The compound of any preceding claim, wherein each of r and s is 3. 23. A compound selected from: , Formula (II) or a salt thereof, wherein: each of Y_a, Y_b, Y_c and Y_d is independently C or O; each of r and s is independently an integer ranging from 1 to 9; R1 is H or C1-C3 alkyl; and each of R2a, R2b, R2c, and R2d is independently C1-C18 alkyl, C2-C18 alkenyl, -(cyclohexyl)-(C1- C₁₈ alkyl), -(cyclohexyl)-(C₂-C₁₈ alkenyl), or -(cyclohexyl)-(CH₂-O-CO)-(C₁-C₁₈ alkyl), wherein the C1-C18 alkyl or C2-C18 alkenyl is optionally substituted with one or more cyclohexyl. 25. The compound of claim 24, wherein each of Ya, Yb, Yc and Yd is C. 26. The compound of claim 24, wherein each of Y_a, Y_b, Y_c and Y_d is O. 27. The compound of any one of claims 24-26, wherein R1 is H. 28. The compound of any one of claims 24-27, wherein each of R_2a, R_2b, R_2c, and R_2d is C₁- C18 alkyl. 29. The compound of any one of claims 24-28, wherein each of R_2a, R_2b, R_2c, and R_2d is C₁- C18 alkyl substituted with one or more cyclohexyl. 30. The compound of any one of claims 24-29, wherein each of R_2a, R_2b, R_2c, and R_2d is . 31. The compound of any one of claims 24-30, wherein each of r and s is 3. 32. A compound selected from: , ,

. 33. A composition comprising at least one lipid nanoparticle comprising at least one compound of Formula (I) of any one of claims 1-23. 34. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 35% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 56% of cholesterol by moles, about 7.5% of DOPC by moles, and about 1.5% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 50:1 (w/w). 35. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 50% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 38.5% of cholesterol by moles, about 10% of DOPC by moles, and about 1.5% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 60:1 (w/w) or about 80:1 (w/w). 36. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 50% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 37.5% of cholesterol by moles, about 10% of DOPC by moles, and about 2.5% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 40:1 (w/w). 37. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 40% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 52.5% of cholesterol by moles, about 5% of DOPC by moles, and about 2.5% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 50:1 (w/w). 38. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 45% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 45.5% of cholesterol by moles, about 7.5% of DOPC by moles, and about 2% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 50:1 (w/w). 39. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 43.17% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 43.17% of cholesterol by moles, about 11.96% of DOPC by moles, and about 1.7% DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 80:1 (w/w). 40. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 45% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 43% of cholesterol by moles, about 10% of DOPC by moles, and about 2% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 80:1 (w/w). 41. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 45% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 46% of cholesterol by moles, about 7.5% of DOPC by moles, and about 1.5% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 60:1 (w/w). 42. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 50% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 39% of cholesterol by moles, about 10% of DOPC by moles, and about 1% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 60:1 (w/w). 43. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 50% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 41.5% of cholesterol by moles, about 7.5% of DOPC by moles, and about 1% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 80:1 (w/w). 44. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 40% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 48.5% of cholesterol by moles, about 10% of DOPC by moles, and about 1.5% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 80:1 (w/w). 45. The composition of claim 33, wherein the at least one lipid nanoparticle comprises about 35% to about 50% of the at least one compound of Formula (I) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 37.5% to about 56% of cholesterol by moles, about 5% to about 12% of DOPC by moles, and about 1% to about 2.5% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 40:1 (w/w) to about 80:1 (w/w). 46. A composition comprising at least one lipid nanoparticle comprising at least one compound of Formula (II) of any one of claims 24-32. 47. The composition of claim 46, wherein the at least one lipid nanoparticle comprises about 35% of the at least one compound of Formula (II) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 59% of cholesterol by moles, about 5% of DOPC by moles, and about 1% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 60:1 (w/w). 48. The composition of claim 46, wherein the at least one lipid nanoparticle comprises about 50% of the at least one compound of Formula (II) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 41.5% of cholesterol by moles, about 7.5% of DOPC by moles, and about 1% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 60:1 (w/w). 49. The composition of claim 46, wherein the at least one lipid nanoparticle comprises about 50% of the at least one compound of Formula (II) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 39% of cholesterol by moles, about 10% of DOPC by moles, and about 1% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 50:1 (w/w). 50. The composition of claim 46, wherein the at least one lipid nanoparticle comprises about 42.5% of the at least one compound of Formula (II) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 51.5% of cholesterol by moles, about 5% of DOPC by moles, and about 1% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 40:1 (w/w). 51. The composition of claim 46, wherein the at least one lipid nanoparticle comprises about 35% to about 50% of the at least one compound of Formula (II) by moles, wherein the at least one nucleic acid molecule comprises at least one RNA molecule and/or at least one DNA molecule, wherein the at least one lipid nanoparticle further comprises: about 37% to about 59% of cholesterol by moles, about 5% to about 10% of DOPC by moles, and about 1% to about 3% of DMG-PEG2000 by moles; and wherein the ratio of lipid to nucleic acid in the at least one nanoparticle is about 50:1 (w/w) to about 80:1 (w/w). 52. The composition of any one of claims 33-51, wherein the RNA molecule is an mRNA molecule, preferably wherein the mRNA molecule further comprises a 5’-CAP. 53. The composition of any one of claims 33-51, wherein the at least one RNA molecule comprises a nucleic acid sequence encoding at least one transposase, preferably wherein the transposase is a piggyBac™ (PB) transposase, a piggyBac-like (PBL) transposase, a Super piggyBac™ (SPB) transposase polypeptide, a Sleeping Beauty transposase, a Hyperactive Sleeping Beauty (SB100X) transposase, a helitron transposase, a Tol2 transposase, a TcBuster transposase or a mutant TcBuster transposase. 54. The composition of any one of claims 33-51, wherein the DNA molecule is a circular DNA molecule, DoggyBone DNA molecule, a DNA plasmid, a DNA nanoplasmid, or a linearized DNA molecule. 55. The composition of any one of claims 33-51, wherein the at least one DNA molecule comprises a nucleic acid sequence encoding at least one transposon. 56. The composition of any one of claims 33-55, wherein the at least one nucleic acid molecule comprises a nucleic acid sequence encoding at least one therapeutic protein. 57. The composition of any one of claims 33-56, wherein the at least one nucleic acid molecule comprises a nucleic acid sequence encoding at least one transposon, wherein the transposon comprises a nucleic acid sequence encoding at least one therapeutic protein. 58. A pharmaceutical composition, comprising the composition of any one of claims 33-57 and at least one pharmaceutically-acceptable excipient or diluent. 59. A method of delivering at least one nucleic acid to at least one cell comprising contacting the at least one cell with at least one composition of any one of claims 33-57. 60. A method of genetically modifying at least one cell comprising contacting the at least one cell with at least one composition of any one of claims 33-57. 61. The method of claims 59 or 60, wherein the at least one cell is a liver cell. 62. The method of claim 61, wherein the liver cell is a hepatocyte, a hepatic stellate cell, Kupffer cell or liver sinusoidal endothelial cell. 63. At least one cell modified according to the method of any one of claims 59-62.

64. A method of treating at least one disease or disorder in a subject in need thereof comprising administering to the subject at least one therapeutically effective amount of the composition of any one of claims 33-57, the pharmaceutical composition of claim 58, or the at least one cell of claim 63. 65. The method of claim 64, wherein the at least one disease or disorder is a liver disease or disorder. 66. The composition of any one of claims 33-57, wherein the at least one RNA molecule comprises a nucleic acid sequence encoding a fusion protein, wherein the fusion protein comprises (i) an inactivated Cas9 (dCas9) protein or an inactivated nuclease domain thereof, (ii) a Clo051 protein or a nuclease domain thereof. 67. The composition of claim 66, wherein the composition further comprises at least one guide RNA molecule.