WO2026062579A1 - Compositions and methods for protein delivery to cells - Google Patents

Abstract

Provided are molecular hooks that are capable of tethering a protein of interest to a high-density lipoprotein (HDL) molecule. Also provided are methods of intracellular protein delivery to cells and organisms using the molecular hooks of the present disclosure. Such methods provide several advantages including the ability to intracellularly deliver the protein of interest to tissues behind the blood-brain barrier, and not requiring extreme cold temperatures for storage or transport.

Description

Atty. Dkt. No.: 139886-2010 COMPOSITIONS AND METHODS FOR PROTEIN DELIVERY TO CELLS CROSS-REFERENCE TO RELATED PATENT APPLICATION [0001] This application claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No.63/696,777, filed September 19, 2024, the entire contents of which are incorporated herein by reference. BACKGROUND [0002] Over the past 20 years, nucleic acid transfection has become a robust and standardized technique for indirectly delivering nucleic acids that encode proteins into cells. However, the direct transfection of proteins (“profection”) remains much more challenging compared to nucleic acid transfection. DNA possesses relatively uniform physicochemical properties, whereas proteins exhibit a wide range of sizes, structures, and charge distributions. Successful protein delivery into cells usually necessitates a chemical linkage between the protein and the transfection reagent. [0003] Due to the highly diverse properties of proteins, a suitable transfection protocol must be developed for each specific type of protein. Additionally, unlike DNA, proteins— especially antibodies—face difficulties in maintaining their tertiary structures when bound to transfection reagents. The present disclosure provides compositions and methods that overcome the difficulties in delivering proteins into cells. SUMMARY OF THE DISCLOSURE [0004] In one aspect, the present disclosure is directed to a method for delivering a protein to a target cell in a subject in need thereof comprising, or alternatively consisting essentially of, or yet further consisting of administering to the subject (i) a protein-high-density lipoprotein (HDL) complex wherein the protein is tethered to the exterior of a high-density lipoprotein (HDL), or (ii) a protein-molecular hook complex, wherein the molecular hook is tethered to the exterior of an HDL molecule, thereby delivering the protein to the target cell in the subject. [0005] In another aspect, the present disclosure relates to a method for intracellular delivery of a protein to a target cell within a subject in need thereof. The method comprises, consists 4906-4947-1849.2 1 Atty. Dkt. No.: 139886-2010 essentially of, or consists of administering to the subject: (i) a protein-high-density lipoprotein (HDL) complex, wherein the protein intended for intracellular delivery is bound to a constitutively present surface protein located on the exterior of the HDL particle; or (ii) a protein-molecular hook complex, wherein the molecular hook, configured to capture the protein of interest, is tethered to the exterior surface of the HDL particle. Through either configuration, the protein is effectively delivered into the cytoplasm of the target cell within the subject. In some embodiments, the protein is delivered into the nucleus of the target cell. [0006] In another aspect, the present disclosure is directed to a method for delivering a protein to a cell comprising, or alternatively consisting essentially of, or yet further consisting of contacting the cells with a protein-high-density lipoprotein (HDL) complex wherein the protein is tethered to the exterior of an HDL, optionally wherein the protein is tethered to the exterior of an HDL through a molecular hook. [0007] In another aspect, the present disclosure is directed to a method for delivering a protein into the interior of a cell. The method comprises, consists essentially of, or consists of contacting the cell with a protein-high-density lipoprotein (HDL) complex, wherein the protein is tethered to the exterior surface of the HDL particle. Optionally, the protein may be tethered to the exterior of the HDL via a molecular hook. [0008] In some embodiments, the contacting is performed in vitro or in vivo. [0009] In some embodiments, the cells of the subject are behind the blood brain barrier of the subject. In some embodiments, the cells of the subject are in the brain or the spine of the subject. [0010] In some embodiments, the molecular hook comprises, or alternatively consists essentially of, or yet further consists of: a first antigen binding domain that specifically binds to an exterior facing protein of the HDL; and a second antigen binding domain that specifically binds to the protein. [0011] In some embodiments, the exterior facing protein is selected from the group consisting of Apolipoprotein A-I (ApoA-I), Apolipoprotein A-II (ApoA-II), Apolipoprotein A-IV (ApoA-IV), Apolipoprotein B (ApoB), Apolipoprotein C-I (ApoC-I), Apolipoprotein C-II (Apo C-II), Apolipoprotein E (Apo E), Apolipoprotein L1 (ApoL-I), Apolipoprotein M 4906-4947-1849.2 2 Atty. Dkt. No.: 139886-2010 (ApoM), Alpha-1-antitrypsin, Alpha-2-HS-glycoprotein, Complement C3, and Serum Amyloid A4. [0012] In some embodiments, the first antigen binding domain specifically binds ApoA-I. In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of a monoclonal antibody produced from a hybridoma of accession No. NITE BP-02442 or accession No. NITE BP-02443. [0013] In some embodiments, the first antigen binding domain specifically binds ApoA-I. In some embodiments, the first antigen binding domain comprises CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 54 SEQ ID NO: 55 SEQ ID NO: 56 SEQ ID NO: 57 SEQ ID NO: 58 SEQ ID NO: 59 . [0014] In some embodiments, the first antigen binding domain comprises a light chain variable region as shown in SEQ ID NO: 52 and a heavy chain variable region as shown in SEQ ID NO: 53. [0015] In some embodiments, the first antigen binding domain specifically binds ApoA-II. In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the EPR2913 monoclonal antibody. In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of amino acid sequences of a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15 SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 SEQ ID NO: 19 SEQ ID NO: 20 SEQ ID NO: 21 SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 . [0016] In some embodiments, the first antigen binding domain specifically binds Apo E. In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of an amino acid sequence selected from: (i) CDR-L1, 4906-4947-1849.2 3 Atty. Dkt. No.: 139886-2010 CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 sequences of the MAB41445 monoclonal antibody; (ii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 25 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 26; (iii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 27 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 28; (iv) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 29 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 30; (v) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 31 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 32; (vi) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 33 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 34; (vii) a light chain variable region as shown in SEQ ID NO: 25 and a heavy chain variable region as shown in SEQ ID NO: 26; (vii) a light chain variable region as shown in SEQ ID NO: 27 and a heavy chain variable region as shown in SEQ ID NO: 28; (vii) a light chain variable region as shown in SEQ ID NO: 29 and a heavy chain variable region as shown in SEQ ID NO: 30; (vii) a light chain variable region as shown in SEQ ID NO: 31 and a heavy chain variable region as shown in SEQ ID NO: 32; or (vii) a light chain variable region as shown in SEQ ID NO: 33 and a heavy chain variable region as shown in SEQ ID NO: 34. [0017] In some embodiments, the first antigen binding domain specifically binds Apo C-II. In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 sequences of the 3E4 monoclonal antibody. [0018] In some embodiments, the first antigen binding domain and/or the second antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of an scFv, an (scFv)₂, an scFvFc, a Fab, a Fab’, a F(ab’)₂, a bispecific antibody or a diabody. [0019] In some embodiments, the molecular hook further comprises, or alternatively consists essentially of, or yet further consists of a linker between the first antigen binding domain and the second antigen binding domain, optionally wherein the linker is an enzymatically cleavable linker, a hydrolysable linker, a pH sensitive linker, a photolabile linker, or a self immolative linker. [0020] In some embodiments, the protein is selected from the group consisting of an enzyme, a toxin, an interferon, a tumor suppressor, a protease, a recombinase, a hormone, and a stem cell transcription factor. 4906-4947-1849.2 4 Atty. Dkt. No.: 139886-2010 [0021] In some embodiments, the protein is an antibody, an scFv, an (scFv)2, an scFvFc, a Fab, a Fab’, a F(ab’)2, a bispecific antibody or a diabody. [0022] In some embodiments, the protein specifically binds a KRAS mutant selected from G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R, A146T, or K117N with respect to SEQ ID NO: 51. [0023] In some embodiments, the protein specifically binds a KRAS G12V mutant and comprises amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 62 SEQ ID NO: 63 SEQ ID NO: 64 SEQ ID NO: 65 SEQ ID NO: 66 SEQ ID NO: 67 . In some embodiments, the protein comprises a light chain variable region as shown in SEQ ID NO: 60 and a heavy chain variable region as shown in SEQ ID NO: 61. In some embodiments, the molecular hook comprises a heavy chain comprising SEQ ID NO: 68 and a light chain that comprises SEQ ID NO: 69. [0024] Another aspect of the disclosure is directed to a method for delivering an antibody or an antigen binding fragment thereof to a target cell in a subject in need thereof comprising, or alternatively consisting essentially of, or yet further consisting of administering to the subject a molecular hook, wherein the molecular hook comprises an antigen binding domain that specifically binds to an exterior facing protein of the HDL; and a payload antibody or an antigen binding fragment thereof, and wherein the molecular hook is tethered to the exterior of an HDL molecule, thereby delivering the payload antibody to the target cell in the subject. [0025] In some embodiments, the exterior facing protein is selected from the group consisting of Apolipoprotein A-I (ApoA-I), Apolipoprotein A-II (ApoA-II), Apolipoprotein A-IV (ApoA-IV), Apolipoprotein B (ApoB), Apolipoprotein C-I (ApoC-I), Apolipoprotein C-II (Apo C-II), Apolipoprotein E (Apo E), Apolipoprotein L1 (ApoL-I), Apolipoprotein M (ApoM), Alpha-1-antitrypsin, Alpha-2-HS-glycoprotein, Complement C3, and Serum Amyloid A4. [0026] In some embodiments, the first antigen binding domain specifically binds ApoA-I and comprises CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that 4906-4947-1849.2 5 Atty. Dkt. No.: 139886-2010 are respectively same as amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of a monoclonal antibody produced from a hybridoma of accession No. NITE BP-02442 or accession No. NITE BP-02443. [0027] In some embodiments, the first antigen binding domain specifically binds ApoA-I and comprises CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising amino acid sequences from a single line of the following table: a light chain variable region as shown in SEQ ID NO: 52 and a heavy chain variable region as shown in SEQ ID NO: 53. [0028] In some embodiments, the first antigen binding domain specifically binds ApoA-II and comprises CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the EPR2913 monoclonal antibody, or amino acid sequences of a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15 SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 SEQ ID NO: 19 SEQ ID NO: 20 SEQ ID NO: 21 SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 . [0029] In some embodiments, the first antigen binding domain specifically binds Apo E. In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of an amino acid sequence selected from: (i) CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 sequences of the MAB41445 monoclonal antibody; (ii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 25 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 26; (iii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 27 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 28; (iv) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 29 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 30; (v) CDR-L1, CDR-L2, and 4906-4947-1849.2 6 Atty. Dkt. No.: 139886-2010 CDR-L3 sequences of SEQ ID NO: 31 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 32; (vi) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 33 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 34; (vii) a light chain variable region as shown in SEQ ID NO: 25 and a heavy chain variable region as shown in SEQ ID NO: 26; (vii) a light chain variable region as shown in SEQ ID NO: 27 and a heavy chain variable region as shown in SEQ ID NO: 28; (vii) a light chain variable region as shown in SEQ ID NO: 29 and a heavy chain variable region as shown in SEQ ID NO: 30; (vii) a light chain variable region as shown in SEQ ID NO: 31 and a heavy chain variable region as shown in SEQ ID NO: 32; or (vii) a light chain variable region as shown in SEQ ID NO: 33 and a heavy chain variable region as shown in SEQ ID NO: 34. [0030] In some embodiments, the first antigen binding domain specifically binds Apo C-II. In some embodiments, the first antigen binding domain comprises CDR-L1, CDR-L2, CDR- L3, CDR-H1, CDR-H2 and CDR-H3 of the 3E4 monoclonal antibody. [0031] In some embodiments, the first antigen binding domain and/or the second antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of an scFv, an (scFv)₂, an scFvFc, a Fab, a Fab’, a F(ab’)₂, a bispecific antibody or a diabody. [0032] In some embodiments, the molecular hook further comprises, or alternatively consists essentially of, or yet further consists of a linker between the first antigen binding domain and the second antigen binding domain, optionally wherein the linker is an enzymatically cleavable linker, a hydrolysable linker, a pH sensitive linker, a photolabile linker, or a self immolative linker. [0033] In some embodiments, the protein is selected from the group consisting of an enzyme, a toxin, an interferon, a tumor suppressor, a protease, a recombinase, a hormone, and a stem cell transcription factor. [0034] In some embodiments, the antigen binding domain and/or the payload antibody or antigen binding fragment thereof comprises an scFv, an (scFv)₂, an scFvFc, a Fab, a Fab’, a F(ab’)2, a bispecific antibody or a diabody. [0035] Another aspect of the disclosure is directed to a molecular hook comprising, or alternatively consisting essentially of, or yet further consisting of: (i) a first antigen binding domain that specifically binds to an exterior facing protein of a high density lipoprotein 4906-4947-1849.2 7 Atty. Dkt. No.: 139886-2010 (HDL); and (ii) a second antigen binding domain that specifically binds to a protein, or a payload antibody or an antigen binding fragment thereof. [0036] In some embodiments, the exterior facing protein is selected from the group consisting of Apolipoprotein A-I (ApoA-I), Apolipoprotein A-II (ApoA-II), Apolipoprotein A-IV (ApoA-IV), Apolipoprotein B (ApoB), Apolipoprotein C-I (ApoC-I), Apolipoprotein C-II (Apo C-II), Apolipoprotein E (Apo E), Apolipoprotein L1 (ApoL-I), Apolipoprotein M (ApoM), Alpha-1-antitrypsin, Alpha-2-HS-glycoprotein, Complement C3, and Serum Amyloid A4. [0037] In some embodiments, the first antigen binding domain specifically binds ApoA-I. In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as amino acid sequences of CDR-L1, CDR- L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of a monoclonal antibody produced from a hybridoma of accession No. NITE BP-02442 or accession No. NITE BP-02443. [0038] In some embodiments, the first antigen binding domain specifically binds ApoA-I. In some embodiments, the first antigen binding domain comprises CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 54 SEQ ID NO: 55 SEQ ID NO: 56 SEQ ID NO: 57 SEQ ID NO: 58 SEQ ID NO: 59 . [0039] In some embodiments, the first antigen binding domain comprises a light chain variable region as shown in SEQ ID NO: 52 and a heavy chain variable region as shown in SEQ ID NO: 53. [0040] In some embodiments, the first antigen binding domain specifically binds ApoA-II. In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the EPR2913 monoclonal antibody, or amino acid sequences of a single line of the following table: 4906-4947-1849.2 8 Atty. Dkt. No.: 139886-2010 CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15 SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 SEQ ID NO: 19 SEQ ID NO: 20 SEQ ID NO: 21 SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 . [0041] In some embodiments, the first antigen binding domain specifically binds Apo E and comprises, or alternatively consists essentially of, or yet further consists of an amino acid sequence selected from: (i) CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 sequences of the MAB41445 monoclonal antibody; (ii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 25 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 26; (iii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 27 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 28; (iv) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 29 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 30; (v) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 31 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 32; (vi) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 33 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 34; (vii) a light chain variable region as shown in SEQ ID NO: 25 and a heavy chain variable region as shown in SEQ ID NO: 26; (vii) a light chain variable region as shown in SEQ ID NO: 27 and a heavy chain variable region as shown in SEQ ID NO: 28; (vii) a light chain variable region as shown in SEQ ID NO: 29 and a heavy chain variable region as shown in SEQ ID NO: 30; (vii) a light chain variable region as shown in SEQ ID NO: 31 and a heavy chain variable region as shown in SEQ ID NO: 32; or (vii) a light chain variable region as shown in SEQ ID NO: 33 and a heavy chain variable region as shown in SEQ ID NO: 34. [0042] In some embodiments, the first antigen binding domain specifically binds Apo C-II. In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the 3E4 monoclonal antibody. [0043] In some embodiments, the first antigen binding domain and/or the second antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of an scFv, an (scFv)2, an scFvFc, a Fab, a Fab’, a F(ab’)2, a bispecific antibody or a diabody. 4906-4947-1849.2 9 Atty. Dkt. No.: 139886-2010 [0044] In some embodiments, wherein the protein is an antibody that specifically binds a KRAS mutant selected from G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R, A146T, or K117N with respect to SEQ ID NO: 51. [0045] In some embodiments, the protein specifically binds a KRAS G12V mutant. In some embodiments, the protein comprises amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 62 SEQ ID NO: 63 SEQ ID NO: 64 SEQ ID NO: 65 SEQ ID NO: 66 SEQ ID NO: 67 . [0046] In some embodiments, the protein comprises a light chain variable region as shown in SEQ ID NO: 60 and a heavy chain variable region as shown in SEQ ID NO: 61. [0047] In some embodiments, the molecular hook comprises a heavy chain and a light chain. In some embodiments, the molecular hook heavy chain comprises SEQ ID NO: 68 and the molecular hook light chain comprises SEQ ID NO: 69. [0048] In some embodiments, the first antigen binding domain and or the second antigen binding domain or the payload antibody or antigen binding fragment thereof comprises an scFv, an (scFv)₂, an scFvFc, a Fab, a Fab’, a F(ab’)₂, a bispecific antibody or a diabody. [0049] In some embodiments, the molecular hook comprises a linker between the first antigen binding domain and the second antigen binding domain or the payload antibody or antigen binding fragment thereof, optionally wherein the linker is an enzymatically cleavable linker, a hydrolysable linker, a pH sensitive linker, a photolabile linker, or a self immolative linker. BRIEF DESCRIPTION OF THE FIGURES [0050] FIGS.1A-1G. (A) Structure of an HDL molecule. HDL molecules are nano sized particles that circulate in the bloodstream. HDL nanoparticles can cross the blood-brain barrier. (B) Schematic of a non-limiting molecular hook example that binds to both Apo A1 and a target protein. In this embodiment, the Apo A1 binding part comprises an anti-Apo A1 antibody, or an antigen binding fragment thereof, and the protein-binding site comprises an antibody or a fragment thereof, that can bind to a target protein that will be delivered into a 4906-4947-1849.2 10 Atty. Dkt. No.: 139886-2010 cell (“the payload”). (C) Schematic of a non-limiting molecular hook example that binds to both Apo CII and protein. In this embodiment, the Apo CII binding part comprises an anti- Apo CII antibody, or an antigen binding fragment thereof, and the protein-binding site comprises an antibody, or an antigen binding fragment thereof, that binds to a target protein that will be delivered into a cell. (D) Schematic of a non-limiting molecular hook example that binds to both Apo A1 and a therapeutic antibody that is desired to be delivered to a cell. In this embodiment, the Apo A1 binding part comprises an anti-Apo A1 antibody, or an antigen binding fragment thereof, and the protein-binding site comprises an antibody, or an antigen binding fragment thereof, that binds to the therapeutic antibody that will be delivered into a cell. (E) Schematic of a non-limiting molecular hook example that binds to both Apo CII and a therapeutic antibody that is desired to be delivered to a cell. In this embodiment, the Apo A1 binding part comprises an anti-Apo CII antibody, or an antigen binding fragment thereof, and the protein-binding site comprises an antibody, or an antigen binding fragment thereof, that binds to the therapeutic antibody that will be delivered into a cell. (F) Schematic of a non-limiting molecular hook example that comprises a binding domain specific to Apo A1 and an antibody that is desired to be delivered to a cell. In this embodiment, the molecular hook comprises: a first Apo A1 binding part, and a second part that comprises an antibody (e.g., a therapeutic antibody), or an antigen binding fragment thereof, that binds to a target protein (the “payload”). (G) Schematic of a non-limiting molecular hook example that comprises a binding domain specific to Apo CII and an antibody that is desired to be delivered to a cell. In this embodiment, the molecular hook comprises: a first Apo CII binding part, and a second part that comprises an antibody (e.g., a therapeutic antibody), or an antigen binding fragment thereof, that binds to a target protein (the “payload”). [0051] FIGS.2A-2E. Internalization of dye-conjugated antibodies. x-axis: fluorescence intensity, y-axis: event count. Shift in fluorescence indicates internalization of the dye- conjugated compound. (A) Internalization of conjugated ApoA-I antibody versus internalization of an isotype control antibody. The conjugated ApoA-I antibody was internalized in over 71% of the cells. (B) Internalization of conjugated ApoA-I antibody as compared to an untreated (no antibody) control, showing 97% signal in cells treated with the conjugated ApoA-I antibody. (C) Time course of conjugated ApoA-I antibody internalization over 24, 48 or 96 hours. Durable internalization was achieved by 96 hours. The rightmost graph (48h + PEI) shows the result of a positive control experiment. In this setup, PEI (polyethylenimine)—a compound known to disrupt cell membrane integrity and to 4906-4947-1849.2 11 Atty. Dkt. No.: 139886-2010 be toxic to virtually all cell types, including both healthy and cancerous cells—was added to the culture medium. Under these conditions, both the control antibody (anti-HEL) and conjugated ApoA-I antibody were internalized in a similar fashion. (D) Quantification of internalization shown in FIG.2C. (E) Time course of conjugated HEL antibody internalization over 24, 48 or 96 hours. HEL targeting antibodies could not cause internalization at any time point. The rightmost graph (48h + PEI) shows the result of a positive control experiment. In this setup, PEI (polyethylenimine)—a compound known to disrupt cell membrane integrity and to be toxic to virtually all cell types, including both healthy and cancerous cells—was added to the culture medium. [0052] FIGS.3A-3B. Testing for endosome trapping. In these experiments, if the internalized antibody is in the endosomes (trapped in the endosomes) there is an increase in red fluorescence due to the pH change. (A) 20 minutes and (B) 93 hours after conjugated ApoA-I antibody and isotype control antibody treatment cells were imaged in phase contrast and red fluorescence channels. In either time point, there were no endosomal trapping. Same cells were used in FACS experiments to show that the conjugated ApoA-I antibody was indeed internalized into the cell. [0053] FIGS.4A-4C. Non-limiting molecular hook configurations. (A) A diabody linked to an Fc-Fab. (B) A whole antibody linked to an scFv. (C) A Whole antibody linked to a protein molecule. Any possible combination of the individual antigen binding domains (e.g., a whole antibody, a diabody, a Fab, an scFv, an Fc-Fab, an (scFv)₂, an scFvFc, a Fab, a Fab’, a F(ab’)2 etc.) is possible and contemplated in this application, as described herein. [0054] FIGS.5A-5B. (A) Monospecific kinetics of molecular hook carrying an antibody specific to mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) protein (KRAS G12V mutant) in the presence of the mutant KRAS protein. The value after Compound-G (500, 250, 125 etc.) indicates the tested concentration value in nM. (B) Monospecific kinetics of molecular hook carrying an antibody specific to mutant KRAS protein (KRAS G12V mutant) in the presence of wild type KRAS protein. [0055] FIGS.6A-6C. (A) Molecular hooks are internalized in MIA-PaCa-2 cells in a concentration-dependent manner. (B) Specificity assessment of the molecular hook in MIA- PaCa-2 cell line. (C) Inhibition of macropinocytosis by EIPA increases molecular hook uptake. 4906-4947-1849.2 12 Atty. Dkt. No.: 139886-2010 [0056] FIGS.7A-7C. (A) Molecular hooks are internalized in CAPAN-2 cells in a concentration-dependent manner. (B) Specificity assessment of the molecular hook in CAPAN-2 cell line. (C) Inhibition of macropinocytosis by EIPA decreases molecular hook uptake in CAPAN-2 cells. DETAILED DESCRIPTION Definitions [0057] As it would be understood, the section or subsection headings as used herein is for organizational purposes only and are not to be construed as limiting and/or separating the subject matter described. [0058] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods, devices, and materials are now described. All technical and patent publications cited herein are incorporated herein by reference in their entirety. Nothing herein is to be construed as an admission that the disclosure is not entitled to antedate such disclosure by virtue of prior disclosure. [0059] The practice of the present disclosure will employ, unless otherwise indicated, conventional techniques of tissue culture, immunology, molecular biology, microbiology, cell biology and recombinant DNA, which are within the skill of the art. See, e.g., Sambrook and Russell eds. (2001) Molecular Cloning: A Laboratory Manual, 3rd edition; the series Ausubel et al. eds. (2007) Current Protocols in Molecular Biology; the series Methods in Enzymology (Academic Press, Inc., N.Y.); MacPherson et al. (1991) PCR 1: A Practical Approach (IRL Press at Oxford University Press); MacPherson et al. (1995) PCR 2: A Practical Approach; Harlow and Lane eds. (1999) Antibodies, A Laboratory Manual; Freshney (2005) Culture of Animal Cells: A Manual of Basic Techique, 5th edition; Gait ed. (1984) Oligonucleotide Synthesis; U.S. Patent No.4,683,195; Hames and Higgins eds. (1984) Nucleic Acid Hybridization; Anderson (1999) Nucleic Acid Hybridization; Hames and Higgins eds. (1984) Transcription and Translation; Immobilized Cells and Enzymes (IRL Press (1986)); Perbal (1984) A Practical Guide to Molecular Cloning; Miller and Calos eds. (1987) Gene Transfer Vectors for Mammalian Cells (Cold Spring Harbor Laboratory); Makrides ed. (2003) Gene 4906-4947-1849.2 13 Atty. Dkt. No.: 139886-2010 Transfer and Expression in Mammalian Cells; Mayer and Walker eds. (1987) Immunochemical Methods in Cell and Molecular Biology (Academic Press, London); Herzenberg et al. eds (1996) Weir’s Handbook of Experimental Immunology; Manipulating the Mouse Embryo: A Laboratory Manual, 3rd edition (Cold Spring Harbor Laboratory Press (2002)); Sohail (ed.) (2004) Gene Silencing by RNA Interference: Technology and Application (CRC Press). [0060] As used in the specification and claims, the singular form “a,” “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a cell” includes a plurality of cells, including mixtures thereof. [0061] As used herein, the term “comprising” is intended to mean that the compounds, agents, compositions and methods include the recited elements, but not exclude others. “Consisting essentially of” when used to define compounds, agents, compositions and methods, shall mean excluding other elements of any essential significance to the combination. Thus, a composition consisting essentially of the elements as defined herein would not exclude trace contaminants, e.g., from the isolation and purification method and pharmaceutically acceptable carriers, preservatives, and the like. “Consisting of” shall mean excluding more than trace elements of other ingredients. Embodiments defined by each of these transition terms are within the scope of this technology. [0062] All numerical designations, e.g., pH, temperature, time, concentration, and molecular weight, including ranges, are approximations which are varied (+) or (-) by increments of 1, 5, or 10%. It is to be understood, although not always explicitly stated that all numerical designations are preceded by the term “about.” It also is to be understood, although not always explicitly stated, that the reagents described herein are merely exemplary and that equivalents of such are known in the art. [0063] The term “about,” as used herein when referring to a measurable value such as an amount or concentration and the like, is meant to encompass variations of 20%, 10%, 5%, 1 %, 0.5%, or even 0.1 % of the specified amount. [0064] As used herein, comparative terms as used herein, such as high, low, increase, decrease, reduce, or any grammatical variation thereof, can refer to certain variation from the reference. In some embodiments, such variation can refer to about 10%, or about 20%, or about 30%, or about 40%, or about 50%, or about 60%, or about 70%, or about 80%, or about 4906-4947-1849.2 14 Atty. Dkt. No.: 139886-2010 90%, or about 1 fold, or about 2 folds, or about 3 folds, or about 4 folds, or about 5 folds, or about 6 folds, or about 7 folds, or about 8 folds, or about 9 folds, or about 10 folds, or about 20 folds, or about 30 folds, or about 40 folds, or about 50 folds, or about 60 folds, or about 70 folds, or about 80 folds, or about 90 folds, or about 100 folds or more higher than the reference. In some embodiments, such variation can refer to about 1%, or about 2%, or about 3%, or about 4%, or about 5%, or about 6%, or about 7%, or about 8%, or about 0%, or about 10%, or about 20%, or about 30%, or about 40%, or about 50%, or about 60%, or about 70%, or about 75%, or about 80%, or about 85%, or about 90%, or about 95%, or about 96%, or about 97%, or about 98%, or about 99% of the reference. [0065] As will be understood by one skilled in the art, for any and all purposes, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Furthermore, as will be understood by one skilled in the art, a range includes each individual member. [0066] “Optional” or “optionally” means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not. [0067] As used herein, “and/or” refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (“or”). [0068] “Substantially” or “essentially” means nearly totally or completely, for instance, 95% or greater of some given quantity. In some embodiments, “substantially” or “essentially” means 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9%. [0069] The terms or “acceptable,” “effective,” or “sufficient” when used to describe the selection of any components, ranges, dose forms, etc. disclosed herein intend that said component, range, dose form, etc. is suitable for the disclosed purpose. [0070] A “composition” is intended to mean a combination of active agent and another compound or composition, inert (for example, a detectable agent or label) or active, such as an adjuvant, diluent, binder, stabilizer, buffers, salts, lipophilic solvents, preservative, adjuvant or the like and include pharmaceutically acceptable carriers. 4906-4947-1849.2 15 Atty. Dkt. No.: 139886-2010 [0071] Carriers also include pharmaceutical excipients and additives proteins, peptides, amino acids, lipids, and carbohydrates (e.g., sugars, including monosaccharides, di-, tri, tetra- oligosaccharides, 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. Exemplary protein excipients include serum albumin such as human serum albumin (HSA), recombinant human albumin (rHA), gelatin, casein, and the like. Representative amino acid components, which can also function in a buffering capacity, include alanine, arginine, glycine, arginine, betaine, histidine, glutamic acid, aspartic acid, cysteine, lysine, leucine, isoleucine, valine, methionine, phenylalanine, aspartame, and the like. Carbohydrate excipients are also intended within the scope of this technology, examples of which include but are not limited to monosaccharides such as fructose, maltose, galactose, glucose, D- mannose, sorbose, and the like; disaccharides, such as lactose, sucrose, trehalose, cellobiose, and the like; polysaccharides, such as raffinose, melezitose, maltodextrins, dextrans, starches, and the like; and alditols, such as mannitol, xylitol, maltitol, lactitol, xylitol sorbitol (glucitol) and myoinositol. [0072] A composition as disclosed herein can be a pharmaceutical composition. A “pharmaceutical composition” is intended to include the combination of an active agent with a carrier, inert or active, making the composition suitable for diagnostic or therapeutic use in vitro, in vivo or ex vivo. [0073] “Pharmaceutically acceptable carriers” refers to any diluents, excipients, or carriers that may be used in the compositions disclosed herein. Pharmaceutically acceptable carriers include ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances, such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, Mack Publishing Company, a standard reference text in this field. They may be selected with respect to the intended form of administration, that is, 4906-4947-1849.2 16 Atty. Dkt. No.: 139886-2010 oral tablets, capsules, elixirs, syrups and the like, and consistent with conventional pharmaceutical practices. [0074] The compositions used in accordance with the disclosure can be packaged in dosage unit form for ease of administration and uniformity of dosage. The term "unit dose" or "dosage" refers to physically discrete units suitable for use in a subject, each unit containing a predetermined quantity of the composition calculated to produce the desired responses in association with its administration, i.e., the appropriate route and regimen. The quantity to be administered, both according to number of treatments and unit dose, depends on the result and/or protection desired. Precise amounts of the composition also depend on the judgment of the practitioner and are peculiar to each individual. Factors affecting dose include physical and clinical state of the subject, route of administration, intended goal of treatment (alleviation of symptoms versus cure), and potency, stability, and toxicity of the particular composition. Upon formulation, solutions are administered in a manner compatible with the dosage formulation and in such amount as is therapeutically or prophylactically effective. The formulations are easily administered in a variety of dosage forms, such as the type of injectable solutions described herein. [0075] A combination as used herein intends that the individual active ingredients of the compositions are separately formulated for use in combination and can be separately packaged with or without specific dosages. The active ingredients of the combination can be administered concurrently or sequentially. [0076] An “effective amount” is an amount sufficient to effect beneficial or desired results. An effective amount can be administered in one or more administrations, applications, or dosages. Such delivery is dependent on a number of variables including the time period for which the individual dosage unit is to be used, the bioavailability of the therapeutic agent, the route of administration, etc. It is understood, however, that specific dose levels of the therapeutic agents disclosed herein for any particular subject depends upon a variety of factors including the activity of the specific agent employed, bioavailability of the agent, the route of administration, the age of the animal and its body weight, general health, sex, the diet of the animal, the time of administration, the rate of excretion, the drug combination, and the severity of the particular disorder being treated and form of administration. In general, one will desire to administer an amount of the agent that is effective to achieve a serum level commensurate with the concentrations found to be effective in vivo. These considerations, as 4906-4947-1849.2 17 Atty. Dkt. No.: 139886-2010 well as effective formulations and administration procedures are well known in the art and are described in standard textbooks. [0077] “Therapeutically effective amount” of an agent refers to an amount of the agent that is an amount sufficient to obtain a pharmacological response; or alternatively, is an amount of the agent that, when administered to a patient with a specified disorder or disease, is sufficient to have the intended effect, e.g., treatment, alleviation, amelioration, palliation or elimination of one or more manifestations of the specified disorder or disease in the patient. A therapeutic effect does not necessarily occur by administration of one dose and may occur only after administration of a series of doses. Thus, a therapeutically effective amount may be administered in one or more administrations. [0078] As used herein, the phrase “derived from” means isolated from, purified from, or engineered from, or any combination thereof. [0079] As used herein, “treating” or “treatment” of a disease in a subject refers to (1) preventing the symptoms or disease from occurring in a subject that is predisposed or does not yet display symptoms of the disease; (2) inhibiting the disease or arresting its development; or (3) ameliorating or causing regression of the disease or the symptoms of the disease. As understood in the art, “treatment” is an approach for obtaining beneficial or desired results, including clinical results. For the purposes of the present technology, beneficial or desired results can include one or more, but are not limited to, alleviation or amelioration of one or more symptoms, diminishment of extent of a condition (including a disease), stabilized (i.e., not worsening) state of a condition (including disease), delay or slowing of condition (including disease), progression, amelioration or palliation of the condition (including disease), states and remission (whether partial or total), whether detectable or undetectable. When the disease is cancer, the following clinical end points are non-limiting examples of treatment: reduction in tumor burden, slowing of tumor growth, longer overall survival, longer time to tumor progression, inhibition of metastasis or a reduction in metastasis of the tumor. In one aspect, treatment excludes prophylaxis. [0080] As used herein, by "subject" or "individual" or "animal" or "patient" or "mammal," is meant any subject, particularly a mammalian subject, for whom diagnosis, prognosis, or therapy is desired. Mammalian subjects include, but are not limited to, humans, domestic animals, farm animals, zoo animals, sport animals, pet animals such as dogs, cats, guinea pigs, rabbits, rats, mice, horses, cattle, cows; primates such as apes, monkeys, orangutans, 4906-4947-1849.2 18 Atty. Dkt. No.: 139886-2010 and chimpanzees; canids such as dogs and wolves; felids such as cats, lions, and tigers; equids such as horses, donkeys, and zebras; bears, food animals such as cows, pigs, and sheep; ungulates such as deer and giraffes; rodents such as mice, rats, hamsters and guinea pigs; and so on. In certain embodiments, the mammal is a human subject. In other embodiments, a subject is a human patient. In a particular embodiment, a subject is a human patient in need of treatment. [0081] In one embodiment, the term “disease” or “disorder” as used herein refers to any alteration in state of the body or of some of the organs, interrupting or disturbing the performance of the functions and/or causing symptoms such as discomfort, dysfunction, distress, or even death to the person afflicted or those in contact with a person. [0082] The term “contacting” means direct or indirect binding or interaction between two or more. A particular example of direct interaction is binding. A particular example of an indirect interaction is where one entity acts upon an intermediary molecule, which in turn acts upon the second referenced entity. Contacting as used herein includes in solution, in solid phase, in vitro, ex vivo, in a cell and in vivo. Contacting in vivo can be referred to as administering, or administration. [0083] “Administration” or “delivery” of an oncolytic virus or a composition containing same can be performed in one dose, continuously or intermittently throughout the course of treatment. Methods of determining the most effective means and dosage of administration are known to those of skill in the art and will vary with the composition used for therapy, the purpose of the therapy, the target cell being treated, and the subject being treated. Single or multiple administrations can be carried out with the dose level and pattern being selected by the treating physician or in the case of animals, by the treating veterinarian. Suitable dosage formulations and methods of administering the agents are known in the art. Route of administration can also be determined and method of determining the most effective route of administration are known to those of skill in the art and will vary with the composition used for treatment, the purpose of the treatment, the health condition or disease stage of the subject being treated, and target cell or tissue. Non-limiting examples of route of administration include oral administration, intraperitoneal, infusion, nasal administration, inhalation, injection, and topical application. In some embodiments, the administration is administration to a tumor microenvironment. In some embodiments, administering or a grammatical variation thereof also refers to more than one doses with certain interval. In some embodiments, the interval is 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 10 days, 2 4906-4947-1849.2 19 Atty. Dkt. No.: 139886-2010 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 1 year or longer. In some embodiments, one dose is repeated for once, twice, three times, four times, five times, six times, seven times, eight times, nine times, ten times or more. [0084] The term administration shall include without limitation, administration by oral, parenteral (e.g., intramuscular, intraperitoneal, intravenous, intravascular, intraperitoneal, intracerebroventricular (ICV), intrathecal, intracisternal injection or infusion, intracranial, ocular, intradermally, percutaneously, subcutaneous injection, or implant), intratumorally, by inhalation spray nasal, intratracheal, vaginal, rectal, sublingual, urethral (e.g., urethral suppository) or topical routes of administration (e.g., gel, ointment, cream, aerosol, etc.) and can be formulated, alone or together, in suitable dosage unit formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants, excipients, and vehicles appropriate for each route of administration. The disclosure is not limited by the route of administration, the formulation or dosing schedule. [0085] An agent of the present disclosure can be administered for therapy by any suitable route of administration. It will also be appreciated that the optimal route will vary with the condition and age of the recipient, and the disease being treated. [0086] Administration or treatment in “combination” refers to administering two agents such that their pharmacological effects are manifest at the same time. Combination does not require administration at the same time or substantially the same time, although combination can include such administrations. [0087] The phrase “first line” or “second line” or “third line” refers to the order of treatment received by a patient. First line therapy regimens are treatments given first, whereas second or third line therapy are given after the first line therapy or after the second line therapy, respectively. [0088] The terms "oligonucleotide" or "polynucleotide" or "portion," or "segment" thereof refer to a stretch of polynucleotide residues which is long enough to use in PCR or various hybridization procedures to identify or amplify identical or related parts of mRNA or DNA molecules. The polynucleotide compositions of this invention include RNA, cDNA, genomic DNA, synthetic forms, and mixed polymers, both sense and antisense strands, and may be chemically or biochemically modified or may contain non-natural or derivatized nucleotide bases, as will be readily appreciated by those skilled in the art. Such modifications include, for example, labels, methylation, substitution of one or more of the naturally occurring 4906-4947-1849.2 20 Atty. Dkt. No.: 139886-2010 nucleotides with an analog, internucleotide modifications such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoamidates, carbamates, etc.), charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.), pendent moieties (e.g., polypeptides), intercalators (e.g., acridine, psoralen, etc.), chelators, alkylators, and modified linkages (e.g., alpha anomeric nucleic acids, etc.). Also included are synthetic molecules that mimic polynucleotides in their ability to bind to a designated sequence via hydrogen bonding and other chemical interactions. Such molecules are known in the art and include, for example, those in which peptide linkages substitute for phosphate linkages in the backbone of the molecule. [0089] As used herein, the term “purified” does not require absolute purity; rather, it is intended as a relative term. Thus, for example, a purified nucleic acid, peptide, protein, biological complexes, cell, virus or other active compound is one that is isolated in whole or in part from proteins or other contaminants. Generally, substantially purified peptides, proteins, biological complexes, cell, virus or other active compounds for use within the disclosure comprise more than 80% of all macromolecular species present in a preparation prior to admixture or formulation of the peptide, protein, biological complex, cell, virus or other active compound with a pharmaceutical carrier, excipient, buffer, absorption enhancing agent, stabilizer, preservative, adjuvant or other co-ingredient in a complete pharmaceutical formulation for therapeutic administration. More typically, the peptide, protein, biological complex, cell, virus or other active compound is purified to represent greater than 90%, often greater than 95% of all macromolecular species present in a purified preparation prior to admixture with other formulation ingredients. In other cases, the purified preparation may be essentially homogeneous, wherein other macromolecular species are not detectable by conventional techniques. [0090] In some embodiments, the term “engineered”, or “recombinant” refers to having at least one modification not normally found in a naturally occurring protein, polypeptide, polynucleotide, strain, wild-type strain or the parental host strain of the referenced species. In some embodiments, the term “engineered” or “recombinant” refers to being synthetized by human intervention. [0091] As used herein, the term “antibody” collectively refers to immunoglobulins or immunoglobulin-like molecules including by way of example and without limitation, IgA, IgD, IgE, IgG (e.g., IgG1, IgG2, IgG3 or IgG4) and IgM, combinations thereof, and similar molecules produced during an immune response in any vertebrate, for example, in mammals 4906-4947-1849.2 21 Atty. Dkt. No.: 139886-2010 such as humans, goats, rabbits, camels and mice, as well as non-mammalian species, such as shark immunoglobulins. As used herein, “antibodies” (includes intact immunoglobulins) and “antigen binding fragments” specifically bind to a molecule of interest (or a group of highly similar molecules of interest) to the substantial exclusion of binding to other molecules (for example, antibodies and antibody fragments that have a binding constant for the molecule of interest that is at least 10³ M^-1 greater, at least 10⁴ M^-1 greater or at least 10⁵ M^-1 greater than a binding constant for other molecules in a biological sample). The term “antibody” also includes genetically engineered forms such as chimeric antibodies (for example, humanized murine antibodies), heteroconjugate antibodies (such as, bispecific antibodies). See also, Pierce Catalog and Handbook, 1994-1995 (Pierce Chemical Co., Rockford, Ill.); Kuby, J., Immunology, 3rd Ed., W.H. Freeman & Co., New York, 1997. [0092] More particularly, antibody refers to a polypeptide ligand comprising at least a light chain immunoglobulin variable region or heavy chain immunoglobulin variable region which specifically recognizes and binds an epitope of an antigen. Antibodies are composed of a heavy and a light chain, each of which has a variable region, termed the variable heavy (VH) region and the variable light (VL) region. Together, the VH region and the VL region are responsible for binding the antigen recognized by the antibody. Typically, an immunoglobulin has heavy (H) chains and light (L) chains interconnected by disulfide bonds. There are two types of light chain, lambda (λ) and kappa (κ). There are five main heavy chain classes (or isotypes) which determine the functional activity of an antibody molecule: IgM, IgD, IgG, IgA and IgE. Each heavy and light chain contains a constant region and a variable region, (the regions are also known as “domains”). In combination, the heavy and the light chain variable regions specifically bind the antigen. Light and heavy chain variable regions contain a “framework” region interrupted by three hypervariable regions, also called “complementarity-determining regions” or “CDRs”. The extent of the framework region and CDRs have been defined (see, Kabat et al., Sequences of Proteins of Immunological Interest, U.S. Department of Health and Human Services, 1991, which is hereby incorporated by reference). The Kabat database is now maintained online. The sequences of the framework regions of different light or heavy chains are relatively conserved within a species. The framework region of an antibody, that is the combined framework regions of the constituent light and heavy chains, largely adopt a β-sheet conformation and the CDRs form loops which connect, and in some cases form part of, the β-sheet structure. Thus, framework regions act to 4906-4947-1849.2 22 Atty. Dkt. No.: 139886-2010 form a scaffold that provides for positioning the CDRs in correct orientation by inter-chain, non-covalent interactions. [0093] The CDRs are primarily responsible for binding to an epitope of an antigen. The CDRs of each chain are typically referred to as CDR1, CDR2, and CDR3, numbered sequentially starting from the N-terminus, and are also typically identified by the chain in which the particular CDR is located. Thus, a VH CDR3 is located in the variable domain of the heavy chain of the antibody in which it is found, whereas a VL CDR1 is the CDR1 from the variable domain of the light chain of the antibody in which it is found. An antibody that binds L1-CAM protein will have a specific VH region and the VL region sequence, and thus specific CDR sequences. Antibodies with different specificities (i.e., different combining sites for different antigens) have different CDRs. Although it is the CDRs that vary from antibody to antibody, only a limited number of amino acid positions within the CDRs are directly involved in antigen binding. These positions within the CDRs are called specificity determining residues (SDRs). “Immunoglobulin-related compositions” as used herein, refers to antibodies (including monoclonal antibodies, polyclonal antibodies, humanized antibodies, chimeric antibodies, recombinant antibodies, multispecific antibodies, bispecific antibodies, etc.,) as well as antibody fragments. An antibody or antigen binding fragment thereof specifically binds to an antigen. [0094] As used herein, the term “antibody-related polypeptide” means antigen-binding antibody fragments, including single-chain antibodies, that can comprise the variable region(s) alone, or in combination, with all or part of the following polypeptide elements: hinge region, CH1, CH2, and CH3 domains of an antibody molecule. Also included in the technology are any combinations of variable region(s) and hinge region, CH1, CH2, and CH3 domains. Antibody-related molecules useful in the present methods, e.g., but are not limited to, Fab, Fab’ and F(ab’)2, Fd, single-chain Fvs (scFv), single-chain antibodies, disulfide- linked Fvs (sdFv) and fragments comprising either a VL or VH domain. Examples include: (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab’)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., Nature 341: 544-546, 1989), which consists of a VH domain; and (vi) an isolated complementarity determining region (CDR). As such “antibody fragments” or “antigen binding fragments” can comprise a portion of a full-length 4906-4947-1849.2 23 Atty. Dkt. No.: 139886-2010 antibody, generally the antigen binding or variable region thereof. Examples of antibody fragments or antigen binding fragments include Fab, Fab', F(ab’)2, and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. [0095] "Bispecific antibody" or “BsAb”, as used herein, refers to an antibody that can bind simultaneously to two targets that have a distinct structure, e.g., two different target antigens, two different epitopes on the same target antigen, or a hapten and a target antigen or epitope on a target antigen. A variety of different bispecific antibody structures are known in the art. In some embodiments, each antigen binding moiety in a bispecific antibody includes VH and/or VL regions; in some such embodiments, the VH and/or VL regions are those found in a particular monoclonal antibody. In some embodiments, the bispecific antibody contains two antigen binding moieties, each including VH and/or VL regions from different monoclonal antibodies. In some embodiments, the bispecific antibody contains two antigen binding moieties, wherein one of the two antigen binding moieties includes an immunoglobulin molecule having VH and/or VL regions that contain CDRs from a first monoclonal antibody, and the other antigen binding moiety includes an antibody fragment (e.g., Fab, F(ab’), F(ab’)₂, Fd, Fv, dAB, scFv, etc.) having VH and/or VL regions that contain CDRs from a second monoclonal antibody. [0096] As used herein, the term “diabody” refers to a small antibody fragment with two antigen-binding sites, which fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VL) in the same polypeptide chain (VH VL). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen binding sites. Diabodies are described more fully in, e.g., EP 404,097; WO 93/11161; and 30 Hollinger et al., Proc. Natl. Acad. Sci. USA, 90: 6444-6448 (1993). [0097] As used herein, the terms “single-chain antibodies” or “single-chain Fv (scFv)” refer to an antibody fusion molecule of the two domains of the Fv fragment, VL and VH. Single- chain antibody molecules may comprise a polymer with a number of individual molecules, for example, dimer, trimer or other polymers. Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic linker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single- chain Fv (scFv)). Bird et al. (1988) Science 242:423-426 and Huston et al. (1988) Proc. Natl. 4906-4947-1849.2 24 Atty. Dkt. No.: 139886-2010 Acad Sci. USA 85:5879-5883. Such single-chain antibodies can be prepared by recombinant techniques or enzymatic or chemical cleavage of intact antibodies. [0098] Any of the above-noted antibody fragments are obtained using conventional techniques known to those of skill in the art, and the fragments are screened for binding specificity and neutralization activity in the same manner as are intact antibodies. [0099] As used herein, an “antigen” refers to a molecule to which an antibody (or antigen binding fragment thereof) can selectively bind. The target antigen may be a protein, carbohydrate, nucleic acid, lipid, hapten, or other naturally occurring or synthetic compound. In some embodiments, the target antigen may be a polypeptide (e.g., a L1-CAM polypeptide). An antigen may also be administered to an animal to generate an immune response in the animal. Such antigens may also be called “immunogen”. [0100] The term “antigen binding fragment” refers to a fragment of the whole immunoglobulin structure which possesses a part of a polypeptide responsible for binding to antigen. Examples of the antigen binding fragment useful in the present technology include scFv, (scFv)2, scFvFc, Fab, Fab’ and F(ab’)2, but are not limited thereto. [0101] By “binding affinity” is meant the strength of the total noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen, a hapten or antigenic peptide). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (Kd). Affinity can be measured by standard methods known in the art, including those described herein. A low-affinity complex contains an antibody that generally tends to dissociate readily from the antigen, whereas a high-affinity complex contains an antibody that generally tends to remain bound to the antigen for a longer duration. [0102] “Homology” or “identity” or “similarity” refers to sequence similarity between two peptides or between two nucleic acid molecules. Homology can be determined by comparing a position in each sequence which may be aligned for purposes of comparison. When a position in the compared sequence is occupied by the same base or amino acid, then the molecules are homologous at that position. A degree of homology between sequences is a function of the number of matching or homologous positions shared by the sequences. A polynucleotide or polynucleotide region (or a polypeptide or polypeptide region) has a certain percentage (for example, at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99%) of “sequence identity” to another sequence means that, when aligned, that percentage of 4906-4947-1849.2 25 Atty. Dkt. No.: 139886-2010 bases (or amino acids) are the same in comparing the two sequences. This alignment and the percent homology or sequence identity can be determined using software programs known in the art. In some embodiments, default parameters are used for alignment. One alignment program is BLAST, using default parameters. In particular, programs are BLASTN and BLASTP, using the following default parameters: Genetic code=standard; filter=none; strand=both; cutoff=60; expect=10; Matrix=BLOSUM62; Descriptions=50 sequences; sort by ═HIGH SCORE; Databases=non-redundant, GenBank+EMBL+DDBJ+PDB+GenBank CDS translations+SwissProtein+SPupdate+PIR. Details of these programs can be found at the National Center for Biotechnology Information. Biologically equivalent polynucleotides are those having the specified percent homology and encoding a polypeptide having the same or similar biological activity. Two sequences are deemed “unrelated” or “non-homologous” if they share less than 40% identity, or less than 25% identity, with each other. [0103] As used herein, the term “humanized” forms of non-human (e.g., murine) antibodies are chimeric antibodies which contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies are human immunoglobulins in which hypervariable region residues of the recipient are replaced by hypervariable region residues from a non-human species (donor antibody) such as mouse, rat, rabbit, camel or nonhuman primate having the desired specificity, affinity, and capacity. In some embodiments, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues which are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance such as binding affinity. Generally, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains (e.g., Fab, Fab’, F(ab’)2, or Fv), in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus FR sequence although the FR regions may include one or more amino acid substitutions that improve binding affinity. The number of these amino acid substitutions in the FR are typically no more than 6 in the H chain, and in the L chain, no more than 3. The humanized antibody optionally may also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature 321:522-525 (1986); Reichmann et al., Nature 332:323-329 (1988); and Presta, Curr. 4906-4947-1849.2 26 Atty. Dkt. No.: 139886-2010 Op. Struct. Biol.2:593-596 (1992). See e.g., Ahmed & Cheung, FEBS Letters 588(2):288- 297 (2014). [0104] As used herein, the term “hypervariable region” refers to the amino acid residues of an antibody which are responsible for antigen-binding. The hypervariable region generally comprises amino acid residues from a “complementarity determining region” or “CDR” (e.g., around about residues 24-34 (L1), 50-56 (L2) and 89-97 (L3) in the VL, and around about 31-35B (H1), 50-65 (H2) and 95-102 (H3) in the VH (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)) and/or those residues from a “hypervariable loop” (e.g., residues 26- 32 (L1), 50-52 (L2) and 91-96 (L3) in the VL, and 26-32 (H1), 52A-55 (H2) and 96-101 (H3) in the VH (Chothia and Lesk J. Mol. Biol.196:901-917 (1987)). [0105] As used herein, the terms “identical” or percent “identity”, when used in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity over a specified region (e.g., nucleotide sequence encoding an antibody described herein or amino acid sequence of an antibody described herein)), when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection, e.g., NCBI web site). Such sequences are then said to be “substantially identical.” This term also refers to, or can be applied to, the complement of a test sequence. The term also includes sequences that have deletions and/or additions, as well as those that have substitutions. In some embodiments, identity exists over a region that is at least about 25 amino acids or nucleotides in length, or 50-100 amino acids or nucleotides in length. [0106] As used herein, the terms “individual,” “patient,” or “subject” can be an individual organism, a vertebrate, a mammal, or a human. In some embodiments, the individual, patient or subject is a human. In some embodiments, the subject is suffering from cancer. [0107] The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that 4906-4947-1849.2 27 Atty. Dkt. No.: 139886-2010 may be present in minor amounts. For example, a monoclonal antibody can be an antibody that is derived from a single clone, including any eukaryotic, prokaryotic, or phage clone, and not the method by which it is produced. A monoclonal antibody composition displays a single binding specificity and affinity for a particular epitope (aka. an “antigenic determinant”). Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring production of the antibody by any particular method. Monoclonal antibodies can be prepared using a wide variety of techniques known in the art including, e.g., but not limited to, hybridoma, recombinant, and phage display technologies. For example, the monoclonal antibodies to be used in accordance with the present methods may be made by the hybridoma method first described by Kohler et al., Nature 256:495 (1975), or may be made by recombinant DNA methods (See, e.g., U.S. Patent No.4,816,567). The “monoclonal antibodies” may also be isolated from phage antibody libraries using the techniques described in Clackson et al., Nature 352:624-628 (1991) and Marks et al., J. Mol. Biol.222:581-597 (1991), for example. [0108] As used herein, the phrase “high density lipoprotein” or “HDL” refers to a lipid- protein complex in human blood which when isolated by ultracentrifugation is found in the density range of d = 1.063 to d = 1.21. In some embodiments, an HDL molecule used in the methods of the present disclosure is a subject’s own HDL (i.e., isolated from the subject). In some embodiments, HDL molecule is a donor HDL (i.e., isolated from a donor). In some embodiments, HDL molecule is a reconstituted (artificial) HDL. In some embodiments, the artificial HDL is commercially available. In some embodiments, HDL is from individuals living in a specific region, such as ApoA-I Milano HDL from Milan. [0109] As used herein “ApoA-I Milano HDL” refers to a naturally occurring mutated variant of the apolipoprotein A1 protein found in human HDL, the lipoprotein particle that carries cholesterol from tissues to the liver and is associated with protection against cardiovascular disease. The ApoA-I protein on the Milano HDL has an arginine to cysteine substitution at position 173. 4906-4947-1849.2 28 Atty. Dkt. No.: 139886-2010 [0110] In some embodiments, an HDL molecule is a “reconstituted HDL” which refers to a complex of human Apolipoprotein A-I and 1-palmitoyl-2-oleoyl phosphatidylcholine prepared at a molar ratio of 1 to 100 by the cholate removal method. Reconstituted HDL is commercially available from RayBiotech, Cat. # MD-26-0020P, raybiotech.com/reconstituted-hdl-md-26-0020p, last accessed April 7, 2024; Fisher Scientific, Cat. # 15929708, fishersci.fi/shop/products/recombinant-human-hdl-protein- 3/15929708, last accessed April 7, 2024. [0111] As used herein, “ApoA-I” or “ApoAI”or “Apo A1” or “ApoA1” refers to a gene encoding a lipid-binding protein (Apolipoprotein A-I) belonging to the apolipoprotein gene family. ApoA-I is the major protein component of high density lipoprotein (HDL) in plasma. (Genecards: APOA1, HGNC: 600, NCBI Gene: 335, Ensembl: ENSG00000118137, OMIM®: 107680, UniProtKB/Swiss-Prot: P02647). [0112] As used herein, “ApoA-II” refers to a gene encoding the second most abundant protein of the high-density lipoprotein particles (Apolipoprotein A-II). (Genecards: APOA1, HGNC: 601, NCBI Gene: 336, Ensembl: ENSG00000158874, OMIM^®: 107670, UniProtKB/Swiss-Prot: P02652). [0113] As used herein, “ApoB” refers to a gene encoding a lipid-binding protein (Apolipoprotein B) belonging to the apolipoprotein gene family. (Genecards: APOB, HGNC: 603 NCBI Gene: 338 Ensembl: ENSG00000084674 OMIM®: 107730 UniProtKB/Swiss- Prot: P04114). [0114] As used herein, “ApoC-I” refers to a gene encoding a lipid-binding protein (Apolipoprotein C-I) belonging to the apolipoprotein gene family. (Genecards: APOC1, HGNC: 607 NCBI Gene: 341 Ensembl: ENSG00000130208 OMIM®: 107710 UniProtKB/Swiss-Prot: P02654). [0115] As used herein, “ApoC-II” refers to a gene encoding a lipid-binding protein (Apolipoprotein C-II) belonging to the apolipoprotein gene family. (Genecards: APOC2, HGNC: 609, NCBI Gene: 344, Ensembl: ENSG00000234906, OMIM®: 608083, UniProtKB/Swiss-Prot: P02655). [0116] As used herein, “ApoE” refers to a gene encoding a protein on the surface of HDL (“Apolipoprotein E” or “Apolipoprotein E3”). (Genecards: APOE, HGNC: 613, NCBI Gene: 348, Ensembl: ENSG00000130203, OMIM®: 107741, UniProtKB/Swiss-Prot: P02649). 4906-4947-1849.2 29 Atty. Dkt. No.: 139886-2010 [0117] As used herein, “ApoL-I” refers to a gene encoding a lipid-binding protein (Apolipoprotein L-I) belonging to the apolipoprotein gene family which binds to ApoA-I. (Genecards: APOL1, HGNC: 618 NCBI Gene: 8542 Ensembl: ENSG00000100342 OMIM®: 603743 UniProtKB/Swiss-Prot: O14791). [0118] As used herein, “ApoM” refers to a gene encoding a lipid-binding protein (Apolipoprotein M) belonging to the apolipoprotein gene family. (Genecards: APOM, HGNC: 13916 NCBI Gene: 55937 Ensembl: ENSG00000204444 OMIM®: 606907 UniProtKB/Swiss-Prot: O95445). [0119] As used herein, “Alpha-1-antitrypsin” or “AAT” refers to a gene encoding a serine protease inhibitor belonging to the serpin superfamily whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. (Genecards: SERPINA1, HGNC: 8941 NCBI Gene: 5265 Ensembl: ENSG00000197249 OMIM®: 107400 UniProtKB/Swiss-Prot: P01009). [0120] As used herein, “Alpha-2-HS-glycoprotein” or “A2HS” refers to a gene encoding a negatively-charged serum glycoprotein that is synthesized by hepatocytes. (Genecards: AHSG, HGNC: 349 NCBI Gene: 197 Ensembl: ENSG00000145192 OMIM®: 138680 UniProtKB/Swiss-Prot: P02765). [0121] As used herein, “Complement C3” refers to a gene in the complement pathway. (Genecards: C3, HGNC: 1318 NCBI Gene: 718 Ensembl: ENSG00000125730 OMIM®: 120700 UniProtKB/Swiss-Prot: P01024). [0122] As used herein, “Serum Amyloid A4” is a gene that encodes a protein found on HDL molecules. (Genecards: SAA4, HGNC: 10516 NCBI Gene: 6291 Ensembl: ENSG00000148965 OMIM^®: 104752 UniProtKB/Swiss-Prot: P35542). [0123] As used herein, the term “exterior” refers to the outer surface. In the context of an HDL molecule, “exterior” refers to the outer surface of the HDL particle, in contact with the aqueous environment of the blood. [0124] As used herein, the term “tethered” means bound, linked, or anchored, either directly via a chemical bond or indirectly through non-covalent interactions, but not embedded deep inside. In some embodiments, a tether refers to a flexible link, meaning the attached molecule is constrained to the surface but can move or orient somewhat relative to it. As used herein, the phrase "tethered to the exterior of the HDL molecule" describes a molecule that is physically attached to HDL’s surface layer (often through interactions with lipids or 4906-4947-1849.2 30 Atty. Dkt. No.: 139886-2010 apolipoproteins), rather than being inside the particle’s hydrophobic core. In some embodiments, the tethering is achieved by a molecular as described herein. [0125] As used herein, the phrase “interior of a target cell” means the internal environment of the specific cell that is being targeted, as opposed to its external surface or the surrounding extracellular space. In some embodiments, the interior of a target cell comprises the cytoplasm of the target cell. In some embodiments, the interior of a target cell comprises the nucleus of the target cell. [0126] As used herein, a “linker” or a “spacer” refers to a chemical moiety that links two groups together. In some embodiments, the linker is a flexible linker. In some embodiments, the linker is selected from SEQ ID NOs: 70-72. The linker can be cleavable or non- cleavable. Cleavable linkers can be hydrolyzable, enzymatically cleavable, pH sensitive, photolabile, or disulfide linkers, among others. In some embodiments, cleavable linkers are cleaved once within the cell. Other linkers include homobifunctional (two identical functional groups) and heterobifunctional (two functional groups that are different from each other) linkers. A “linking group” is a functional group capable of forming a covalent linkage consisting of one or more bonds to a bioactive agent. [0127] As used herein, a “hydrolyzable linker” refers to a chemical linkage or bond, such as a covalent bond, that undergoes hydrolysis under physiological conditions. The tendency of a bond to hydrolyze may depend not only on the general type of linkage connecting two central atoms between which the bond is severed, but also on the substituents attached to these central atoms. Non-limiting examples of hydrolytically susceptible linkages include esters of carboxylic acids, phosphate esters, acetals, ketals, acyloxyalkyl ether, imines, orthoesters, and some amide linkages. [0128] As used herein, an “enzymatically cleavable linker” refers to a linkage that is subject to degradation by one or more enzymes. Some hydrolytically susceptible linkages may also be enzymatically degradable. For example, esterases may act on esters of carboxylic acid or phosphate esters, and proteases may act on peptide bonds and some amide linkages. [0129] As used herein, a “pH sensitive linker” refers to a linkage that is stable at one pH and subject to degradation at another pH. For example, the pH sensitive linker can be stable at neutral or basic conditions, but labile at mildly acidic conditions. [0130] As used herein, a “Photolabile linker” refers to a linkage, such as a covalent bond, that cleaves upon exposure to light. The photolabile linker includes an aromatic moiety in order to 4906-4947-1849.2 31 Atty. Dkt. No.: 139886-2010 absorb the incoming light, which then triggers a rearrangement of the bonds in order to cleave the two groups linked by the photolabile linker. [0131] As used herein, a “Self-immolative” or “double prodrug linker” refers to a linkage in which the main function of the linker is to release a functional agent only after selective trigger activation (for example, a drop in pH or the presence of a tissue-specific enzyme) followed by spontaneous chemical breakdown to release the functional agent. [0132] In some embodiments, the payload is tethered (i.e., covalently linked) to an HDL molecule using a linker. In some embodiments, the linker is an enzymatically cleavable linker, a hydrolysable linker, a pH sensitive linker, a photolabile linker, or a self immolative linker. In some embodiments, the linker is severed once within the cell, releasing the payload from the HDL molecule. [0133] As used herein, “SpyCatcher-SpyTag system” refers to a protein ligation method based on a modified domain from a Streptococcus pyogenes surface protein (SpyCatcher), which recognizes a cognate 13-amino-acid peptide (SpyTag). Upon recognition, the two form a covalent isopeptide bond between the side chains of a lysine in SpyCatcher and an aspartate in SpyTag. (as described in Hatlem, Daniel, et al. "Catching a SPY: using the SpyCatcher- SpyTag and related systems for labeling and localizing bacterial proteins." International journal of molecular sciences 20.9 (2019): 2129, incorporated herein in its entirety). [0134] As used herein, the terms “messenger RNA” or “mRNA” refer to any polynucleotide which encodes a polypeptide of interest and which is capable of being translated to produce the encoded polypeptide of interest in vitro, in vivo, in situ, or ex vivo. Traditionally, the basic components of an mRNA molecule include a coding region (“an open reading frame”), a 5’UTR, a 3’UTR, a 5’ cap, and a poly-A tail. [0135] As used herein, the terms “modified messenger RNA” or “modified mRNA” refer to mRNA polynucleotides that include naturally occurring and/or non-naturally occurring modifications, for example, of a sugar, a nucleobase, or an internucleoside linkage (e.g., to a linking phosphate, to a phosphodiester linkage, or to the phosphodiester backbone). Non- natural modified nucleotides may be introduced during synthesis of post-synthesis of the polynucleotides to achieve desired functions or properties. The modifications may be present on an internucleoside linkage, purine or pyrimidine base, or sugar. The modification may be introduced with chemical synthesis or with a polymerase enzyme at the terminal of a chain or 4906-4947-1849.2 32 Atty. Dkt. No.: 139886-2010 anywhere else in the chain. Any of the regions of a polynucleotide may be chemically modified. [0136] As used herein, the term “open reading frame,” abbreviated as “ORF,” refers to a segment or region of an mRNA molecule that encodes a polypeptide. The ORF comprises a continuous stretch of non-overlapping, in-frame codons, beginning with the initiation codon and ending with a stop codon, and is translated by the ribosome. [0137] As used herein, the term “sequence optimization” refers to a process or series of processes by which nucleobases in a reference nucleic acid sequence are replaced with alternative nucleobases, resulting in a nucleic acid sequence with improved properties, e.g., improved protein expression or decreased immunogenicity of the nucleic acid itself. [0138] In general, the goal in sequence optimization is to produce a synonymous nucleotide sequence than encodes the same polypeptide sequence encoded by the reference nucleotide sequence. Thus, there are no amino acid substitutions (as a result of codon optimization) in the polypeptide encoded by the codon optimized nucleotide sequence with respect to the polypeptide encoded by the reference nucleotide sequence. [0139] As used herein, the term “in vivo” refers to events that occur within an organism (e.g., animal, plant, or microbe or cell or tissue thereof). [0140] As used herein, the term “ex vivo” refers to events that occur outside of an organism (e.g., animal, plant, or microbe or cell or tissue thereof). Ex vivo events may take place in an environment minimally altered from a natural (e.g., in vivo) environment. [0141] As used herein, “CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising amino acid sequences that are respectively same as the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of X (X is a monoclonal antibody or an antibody sequence)” means that CDR-L1 is the same as CDR-L1 of X, CDR- L2 is the same as CDR-L2 of X, CDR-L3 is the same as CDR-L3 of X, CDR-H1 is the same as CDR-H1 of X, CDR-H2 is the same as CDR-H2 of X, and CDR-H3 is the same as CDR- H3 of X. Modes for Carrying Out the Disclosure [0142] The present disclosure is based on the Applicant’s surprising finding that proteins and antibodies can be efficiently delivered to a cell in their native confirmations while tethered to the exterior of an HDL molecule. Applicant also developed molecular hooks which can bind 4906-4947-1849.2 33 Atty. Dkt. No.: 139886-2010 to a protein outside of an HDL molecule and a target protein to be delivered (“the payload”) at the same time, effectively tethering the payload to the exterior of the HDL molecule. In some embodiments, the payload is a biologic drug (e.g., an antibody, an enzyme, a hormone, a toxin, etc.). [0143] Applicant surprisingly found that the disclosed molecular hooks can deliver proteins and antibodies to cells in their functional native forms. While conventional protein delivery methods are unable to cross the blood-brain barrier, a protein/antibody payload tethered to an HDL molecule using the disclosed molecular hooks can easily cross the blood-brain barrier and deliver the payload to previously inaccessible central nervous system cells and tissues. Also, the molecular hooks disclosed herein are extremely efficient at delivering a protein to a cancer cell. [0144] Active delivery of therapeutic enzymes, blocking antibodies or proteins (and even peptides) that are able to inhibit signaling proteins governing cell proliferation into the cell using the molecular hooks described herein presents a new paradigm in medical treatment that could potentially revolutionize the field. The significance of this discovery lies in the fact that proteins cannot naturally enter cells due to the lipid-bilayer composition of cell membranes. It is known that proteins can only enter the cell via receptor-mediated endocytosis if a specific receptor for that protein exists on the cell membrane. However, in this case, the protein (whether it be an enzyme or a blocking antibody) is internalized into the endosome, where it is subsequently degraded and rendered inactive. [0145] For the first time, Applicant was able to release a desired protein from the endosomal trap and successfully deliver it into the cell in its fully active form. This is achieved without the use of synthetic lipid particles, but rather by utilizing the body’s own high-density lipoproteins (HDLs) to deliver proteins (which could be enzymes or blocking antibodies) into the cell. Mode of action: the protein is tethered to the surface of the HDL, e.g., using the molecular hooks described herein, enabling the complex to enter the cell intact. HDL, unlike synthetic nanoparticles, avoids being trapped in the endosome and releases its cargo inside the cell. Moreover, after delivering its payload, HDL, which is a natural lipid nanoparticle, exits the cell and re-enters circulation without accumulating in the cell, as synthetic lipid nanoparticles might. Molecular hooks 4906-4947-1849.2 34 Atty. Dkt. No.: 139886-2010 [0146] An aspect of the disclosure is directed to molecular hooks that are capable of tethering a protein (“payload”) to an HDL molecule (“HDL”). The molecular hooks described herein can be used to transfer and deliver proteins into cells. The presently described molecular hooks are superior to the conventional methods of RNA delivery because (i) they can cross the blood-brain barrier “hitchhiking” on HDL molecules; (ii) they can deliver proteins to tumor cells; and (iii) unlike lipid nanoparticle (LNP) delivery, they do not require ultra cold (e.g., -50^oC) for storage or transport (which would save money and make protein biologics easier to transport and store – improving patient accessibility to these therapies). [0147] In some embodiments, the present molecular hooks are pre-loaded with a protein (e.g., a biological drug like an antibody, an enzyme, a hormone or a toxin) (also called the “payload”), forming a protein-molecular hook complex. When the protein-molecular hook complex is administered to a subject, the complex will find and bind HDL molecules in the subject’s bloodstream. This is called “spontaneous self-assembly.” The HDL- protein- molecular hook complex travels through the subject’s bloodstream and can traverse into, and deliver the protein of interest into, many tissues including the central nervous system behind the blood-brain barrier and a variety of tumor cells. [0148] In some embodiments, HDL-protein-molecular hook complexes are prepared ex vivo, e.g., by mixing isolated HDL molecules with the molecular hook and the protein of interest. In some embodiments, HDL-protein-molecular hook complexes administered to a subject or contacted with a cell. [0149] In some embodiments, the molecular hooks of the present disclosure are used in methods for delivering a protein to cells and organisms. In some embodiments, the molecular hooks comprise a plurality of antigen binding domains that bind to both a protein and HDL. [0150] In some embodiments, the molecular hook comprises, or alternatively consists essentially of, or yet further consists of: a first antigen binding domain that specifically binds to an exterior facing protein of the HDL; and a second antigen binding domain that specifically binds to a protein to be delivered (the payload). Some non-limiting examples of such molecular hook designs are shown in FIGS.1B-1E and 4A-4C. [0151] In some embodiments, the payload is a biologic drug selected from an antibody, an enzyme (e.g., an enzyme which can be used to treat a genetic disease which lacks the enzyme), a toxin (e.g., a toxin that can kill a tumor cell), an interferon, a tumor suppressor, a 4906-4947-1849.2 35 Atty. Dkt. No.: 139886-2010 protease, a recombinase, a hormone, or a transcription factor (e.g., a stem cell transcription factor). [0152] In some embodiments, the payload is an antibody, or an antigen binding fragment thereof. In some embodiments, the antibody, or an antigen binding fragment thereof is human or humanized. In some embodiments, the molecular hook comprises an antigen binding domain that specifically binds to an exterior facing protein of the HDL; and a payload antibody or an antigen binding fragment thereof. Some non-limiting examples of such molecular hook designs are shown in FIGS.1F-1G and 4A-4C. [0153] In some embodiments, the exterior facing protein is selected from the group consisting of Apolipoprotein A-I (ApoA-I), Apolipoprotein A-II (ApoA-II), Apolipoprotein E (Apo E) and Apolipoprotein C-II (Apo C-II). [0154] In some embodiments, the first antigen binding domain specifically binds ApoA-I and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of a monoclonal antibody produced from a hybridoma of accession No. NITE BP-02442 or a monoclonal antibody produced from a hybridoma of accession No. NITE BP-02443. In some embodiments, the ApoA-I antibody is an antibody described in US20200018755A1, which is incorporated in its entirety. [0155] In some embodiments, the first antigen binding domain specifically binds ApoA-I and comprises CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 54 SEQ ID NO: 55 SEQ ID NO: 56 SEQ ID NO: 57 SEQ ID NO: 58 SEQ ID NO: 59 , or a light chain variable region as shown in SEQ ID NO: 52 and a heavy chain variable region as shown in SEQ ID NO: 53. [0156] In some embodiments, the first antigen binding domain specifically binds ApoA-II and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as 4906-4947-1849.2 36 Atty. Dkt. No.: 139886-2010 amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of an ApoA-II antibody described in US20160245815A1, or the ApoA-II antibody EPR2913 from Abcam (Catalog No. ab92478, abcam.com/products/primary-antibodies/apolipoprotein-a- iiapoa-ii-antibody-epr2913-ab92478.html, last accessed April 8, 2024). In some embodiments, the first antigen binding domain that specifically binds to ApoA-II comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15 SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 SEQ ID NO: 19 SEQ ID NO: 20 SEQ ID NO: 21 SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 . [0157] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of an ApoE antibody described in US20190270794A1, or the ApoE3 antibody from Bio-techne R&D (Catalog No. MAB41445, bio-techne.com/p/antibodies/human-apolipoprotein-e3- apoe3-antibody-377109_mab41445, last accessed April 8, 2024). [0158] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 25. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 26. In some embodiments, the 4906-4947-1849.2 37 Atty. Dkt. No.: 139886-2010 first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 25 and a heavy chain variable region as shown in SEQ ID NO: 26. [0159] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 27. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 28. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 27 and a heavy chain variable region as shown in SEQ ID NO: 28. [0160] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 29. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 30. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 29 and a heavy chain variable region as shown in SEQ ID NO: 30. [0161] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 31. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 32. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 31 and a heavy chain variable region as shown in SEQ ID NO: 32. 4906-4947-1849.2 38 Atty. Dkt. No.: 139886-2010 [0162] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 33. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 34. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 33 and a heavy chain variable region as shown in SEQ ID NO: 34. [0163] In some embodiments, the first antigen binding domain that specifically binds to ApoA-E comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 35 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 39 SEQ ID NO: 40 SEQ ID NO: 41 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 42 SEQ ID NO: 43 SEQ ID NO: 44 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 45 SEQ ID NO: 46 SEQ ID NO: 41 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 47 SEQ ID NO: 48 SEQ ID NO: 49 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 50 SEQ ID NO: 46 [0164] In some embodiments, the first antigen binding domain specifically binds ApoC-II and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of 3E4 monoclonal ApoC-II antibody from Thermo Fisher (Catalog No. H00000344-M01, thermofisher.com/antibody/product/APOC2-Antibody-clone-3E4-Monoclonal/H00000344- M01, last accessed April 8, 2024). Alternative sources of ApoC-II antibodies which can be 4906-4947-1849.2 39 Atty. Dkt. No.: 139886-2010 used in the present molecular hooks and methods include: LS Bio (Catalog No. LS-B10603- 0.25, lsbio.com/antibodies/ihc-plus-apoc2-antibody-apolipoprotein-c-ii-antibody-elisa-ihc-ip- wb-western-ls-b10603/295268?trid=247, last accessed April 8, 2024), R&D Systems (Catalog No. AF4497-SP, rndsystems.com/products/human-apolipoprotein-c-ii-apoc2- antibody_af4497, last accessed April 8, 2024), OriGene (Catalog No. TA357157, origene.com/catalog/antibodies/primary-antibodies/ta357157/apolipoprotein-cii-apoc2-rabbit- polyclonal-antibody, last accessed April 8, 2024), and other antibodies listed in Genecards APOC2 page at genecards.org/cgi-bin/carddisp.pl?gene=APOC2, last accessed April 8, 2024). [0165] In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of an scFv, an (scFv)2, an scFvFc, a Fab, a Fab’, a F(ab’)2, a bispecific antibody or a diabody. In some embodiments, the second antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of an scFv, an (scFv)2, an scFvFc, a Fab, a Fab’, a F(ab’)2, a bispecific antibody or a diabody. [0166] In some embodiments, the molecular hook comprises, or alternatively consists essentially of, or yet further consists of a linker between the first antigen binding domain and the second antigen binding domain, optionally wherein the linker is an enzymatically cleavable linker, a hydrolysable linker, a pH sensitive linker, a photolabile linker, or a self immolative linker. In some embodiments, the linker between the first antigen binding domain and the second antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of a linker from Spycatcher-Spytag system as described in Hatlem, Daniel, et al. " International journal of molecular sciences 20.9 (2019): 2129, which is incorporated herein in its entirety. Payload [0167] As used herein, “payload” refers to a protein that is intended to be delivered into a cell using the molecular hooks described herein. A payload can be any protein of interest. In some embodiments, the payload is a protein that the target cell lacks. In some embodiments, the payload is a gene editing system, such as a CRISPR-Cas system, or a component thereof. [0168] In some embodiments, the payload is a biological drug. In some embodiments, the biological drug comprises an antibody, or an antigen binding fragment thereof, a toxin, an 4906-4947-1849.2 40 Atty. Dkt. No.: 139886-2010 enzyme, an interferon, a tumor suppressor, a protease, a recombinase, a hormone, or transcription factor (e.g., a stem cell transcription factor). In some embodiments, the antibody, or an antigen fragment thereof is human or humanized. [0169] In some embodiments, the payload is an antibody, optionally a human or humanized antibody, that specifically binds to a mutated protein found in cancer. [0170] In some embodiments, the payload antibody specifically binds to mutated KRAS. In some embodiments, the KRAS mutation is selected from one or more of G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R, A146T, K117N, or any combination thereof, wherein the wild type KRAS sequence is as shown in SEQ ID NO: 51. Antibodies and antibody fragments that are specific for specific mutant KRAS proteins are known in the art, e.g., as disclosed in US20180086832A1 and US20220177603A1, which are incorporated herein in their entireties. [0171] In some embodiments, the protein specifically binds a KRAS G12V mutant and comprises amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 62 SEQ ID NO: 63 SEQ ID NO: 64 SEQ ID NO: 65 SEQ ID NO: 66 SEQ ID NO: 67 , or [0172] a light chain variable region as shown in SEQ ID NO: 60 and a heavy chain variable region as shown in SEQ ID NO: 61. [0173] In some embodiments, the molecular hook is a tetravalent construct that comprises a heavy chain comprising SEQ ID NO: 68 and a light chain that comprises SEQ ID NO: 69. In some embodiments, the heavy chain comprises an amino acid sequence that is at least 90%, 93%, 95%, 97%, or 99% identical to the sequence as shown in SEQ ID NO: 68. In some embodiments, the heavy chain consists of or consists essentially of an amino acid sequence as shown in SEQ ID NO: 68. In some embodiments, the light chain comprises an amino acid sequence that is at least 90%, 93%, 95%, 97%, or 99% identical to the sequence as shown in SEQ ID NO: 69. In some embodiments, the light chain consists of or consists essentially of an amino acid sequence as shown in SEQ ID NO: 69. Methods for delivering Protein into cells and Methods of Treatment [0174] An aspect of the disclosure is directed to an in vivo method for delivering protein to cells of a subject in need thereof comprising, or alternatively consisting essentially of, or yet 4906-4947-1849.2 41 Atty. Dkt. No.: 139886-2010 further consisting of administering to the subject a protein-HDL complex wherein the protein is tethered to the exterior of a high-density lipoprotein (HDL). [0175] Another aspect of the disclosure is directed to a method for intracellular delivery of a protein to a target cell in a subject in need thereof comprising administering to the subject (i) a protein-high-density lipoprotein (HDL) complex wherein the protein is tethered to the exterior of a high-density lipoprotein (HDL), or (ii) a protein-molecular hook complex, wherein the molecular hook is tethered to the exterior of an HDL molecule, wherein the protein is delivered intracellularly together with the HDL molecule. [0176] Another aspect of the disclosure is directed to an in vivo method for delivering protein to cells of a subject in need thereof comprising, or alternatively consisting essentially of, or yet further consisting of administering to the subject a protein-molecular hook complex wherein the molecular hook is as described herein and is capable of tethering to the exterior of any HDL molecule. [0177] Another aspect of the disclosure is directed to a method for delivering a protein into the interior of a cell comprising contacting the cells with a protein-high-density lipoprotein (HDL) complex wherein the protein is tethered to the exterior of an HDL, optionally wherein the protein is tethered to the exterior of an HDL through a molecular hook. [0178] Another aspect of the disclosure is directed to a method for treating a subject in need thereof comprising, or alternatively consisting essentially of, or yet further consisting of administering to the subject a protein-molecular hook complex wherein the molecular hook is as described herein and is capable of tethering to the exterior of any HDL molecule. [0179] Several further aspects of the invention relate to correcting defects associated with a wide range of genetic diseases which are further described on the website of the National Institutes of Health under the topic subsection Genetic Disorders (website at health.nih.gov/topic/GeneticDisorders). [0180] In some embodiments, the disclosure is directed to a method for treating a genetic metabolic disease (aka “an inherited metabolic disease”) in a subject, wherein the genetic metabolic disease is caused by inactivation or loss of a single enzyme in the subject, comprising, or alternatively consisting essentially of, or yet further consisting of administering to the subject a protein-molecular hook complex wherein the molecular hook is as described herein and is capable of tethering to the exterior of any HDL molecule and wherein the protein compensates for the inactivation or loss of the single enzyme in the 4906-4947-1849.2 42 Atty. Dkt. No.: 139886-2010 subject. In some embodiments, the genetic metabolic disease is selected from Phenylketonuria (PKU), Maple Syrup Urine Disease, Gaucher Disease, Tay-Sachs Disease, Ornithine Transcarbamylase Deficiency, or Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency. [0181] Another aspect of the disclosure is directed to a method for treating cancer in a subject in need thereof comprising, or alternatively consisting essentially of, or yet further consisting of administering to the subject a protein-molecular hook complex wherein the molecular hook is as described herein and is capable of tethering to the exterior of any HDL molecule and wherein the protein kills the cancer cell or stops its proliferation. In some embodiments, the protein that kills the cancer cell or stops its proliferation is a toxin. In some embodiments, the protein that kills the cancer cell or stops its proliferation is an antibody (or an antigen binding fragment thereof) that disrupts the signaling within the cancer cell (e.g., an antibody against a mutated oncogene within the cancer cell). [0182] The molecular hooks and/or protein-HDL complexes as described herein are useful in the preparation of medicaments to deliver proteins to cells and treat various diseases as described herein. [0183] In some embodiments, the subject suffers from a single gene disorder (i.e., the disease is a disease caused by a mutation in one gene) and the protein delivered on HDL using molecular hooks makes up for the deficiency from the single gene disorder (e.g., provides a missing enzyme, hormone, metabolite etc.). In some embodiments, the disease is selected from spinal muscular atrophy (SMA), Cystic fibrosis, Marfan syndrome, Huntington’s Disease, alpha thalassemia, beta thalassemia, sickle cell anemia, Fragile X syndrome, or hemochromatosis.. In some embodiments, the subject suffers from cancer, malaria, tuberculosis, Hepatitis A, Hepatitis B, Hepatitis C, HIV/AIDS, rabies, influenza, or COVID- 19. [0184] In some embodiments, the subject suffers from a cancer driven by a KRAS mutation. KRAS (Kirsten rat sarcoma viral oncogene homolog) is a small GTPase in the RAS family. It acts as a molecular switch in cell-signaling pathways that control proliferation and survival. Point mutations, especially in codons 12, 13, 61, 117, and 146, lock KRAS in an “on” state, driving uncontrolled cell growth. KRAS mutations (including G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R, A146T, K117N mutations relative to WT KRAS as shown in SEQ ID NO: 51) are well-known driver mutations in many cancers. 4906-4947-1849.2 43 Atty. Dkt. No.: 139886-2010 [0185] In some embodiments, the cancer driven by a KRAS mutation is selected from pancreatic ductal adenocarcinoma, colorectal cancer, non-small cell lung cancer, cholangiocarcinoma, appendiceal carcinoma, gallbladder carcinoma, small intestine adenocarcinoma, endometrial carcinoma, ovarian mucinous carcinoma, juvenile myelomonocytic leukemia, myelodysplastic syndromes, acute myeloid leukemia, or chronic myelomonocytic leukemia. [0186] In some embodiments, the molecular hook is administered locally to a tumor site. In some embodiments, the molecular hook is administered systemically. In some embodiments, the molecular hook is administered by intravenous (IV) infusion, intravenous bolus injection, subcutaneous (SC) injection, intramuscular (IM) injection, or intraperitoneal (IP) injection. [0187] Another aspect of the disclosure is directed to a method for delivering protein to a cell comprising, or alternatively consisting essentially of, or yet further consisting of contacting the cells with a protein-HDL complex wherein the protein is tethered to the exterior of an HDL. In some embodiments, the contacting is performed in vitro or in vivo. In some embodiments, the protein is tethered to the exterior of an HDL through a molecular hook, wherein the molecular hook is as described herein. In some embodiments, the binding of protein to the molecular hook prevents the degradation or denaturation of the protein during transport and delivery to a target cell or tissue. [0188] In some embodiments, the HDL molecule is the native HDL of a subject. In some embodiments, the HDL molecule is from a donor. In some embodiments, the HDL molecule is selected from a native HDL, an ApoA-I Milano HDL, or a reconstituted HDL. [0189] In some embodiments, the cells of the subject are behind the blood brain barrier of the subject. In some embodiments, the cells of the subject are in the brain or the spine of the subject. [0190] In some embodiments, the molecular hook comprises, or alternatively consists essentially of, or yet further consists of: a first antigen binding domain that specifically binds to an exterior facing protein of the HDL; and a second antigen binding domain that specifically binds to the protein. [0191] In some embodiments, the exterior facing protein is selected from the group consisting of Apolipoprotein A-I (ApoA-I), Apolipoprotein A-II (ApoA-II), Apolipoprotein E (Apo E) and Apolipoprotein C-II (Apo C-II). 4906-4947-1849.2 44 Atty. Dkt. No.: 139886-2010 [0192] In some embodiments, the first antigen binding domain specifically binds ApoA-I and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of a monoclonal antibody produced from a hybridoma of accession No. NITE BP-02442 or a monoclonal antibody produced from a hybridoma of accession No. NITE BP-02443. In some embodiments, the ApoA-I antibody is an antibody described in US20200018755A1, which is incorporated in its entirety. [0193] In some embodiments, the first antigen binding domain specifically binds ApoA-I and comprises CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 54 SEQ ID NO: 55 SEQ ID NO: 56 SEQ ID NO: 57 SEQ ID NO: 58 SEQ ID NO: 59 , or a light chain variable region as shown in SEQ ID NO: 52 and a heavy chain variable region as shown in SEQ ID NO: 53. [0194] In some embodiments, the first antigen binding domain specifically binds ApoA-II and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of an ApoA-II antibody described in US20160245815A1, or the ApoA-II antibody EPR2913 from Abcam (Catalog No. ab92478, abcam.com/products/primary-antibodies/apolipoprotein-a- iiapoa-ii-antibody-epr2913-ab92478.html, last accessed April 8, 2024). In some embodiments, the first antigen binding domain that specifically binds to ApoA-II comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 4906-4947-1849.2 45 Atty. Dkt. No.: 139886-2010 SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15 SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 SEQ ID NO: 19 SEQ ID NO: 20 SEQ ID NO: 21 SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 . [0195] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of an ApoE antibody described in US20190270794A1, or the ApoE3 antibody from Bio-techne R&D (Catalog No. MAB41445, bio-techne.com/p/antibodies/human-apolipoprotein-e3- apoe3-antibody-377109_mab41445, last accessed April 8, 2024). [0196] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 25. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 26. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 25 and a heavy chain variable region as shown in SEQ ID NO: 26. [0197] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 27. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 28. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists 4906-4947-1849.2 46 Atty. Dkt. No.: 139886-2010 essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 27 and a heavy chain variable region as shown in SEQ ID NO: 28. [0198] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 29. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 30. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 29 and a heavy chain variable region as shown in SEQ ID NO: 30. [0199] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 31. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 32. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 31 and a heavy chain variable region as shown in SEQ ID NO: 32. [0200] In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR- L2, and CDR-L3 that are respectively same as amino acid sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 33. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of CDR-H1, CDR-H2 and CDR-H3 that are respectively same as amino acid sequences of CDR-H1, CDR-H2 and CDR-H3 of SEQ ID NO: 34. In some embodiments, the first antigen binding domain specifically binds ApoE and comprises, or alternatively consists essentially of, or yet further consists of a light chain variable region as shown in SEQ ID NO: 33 and a heavy chain variable region as shown in SEQ ID NO: 34. 4906-4947-1849.2 47 Atty. Dkt. No.: 139886-2010 [0201] In some embodiments, the first antigen binding domain that specifically binds to ApoA-E comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 35 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 39 SEQ ID NO: 40 SEQ ID NO: 41 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 42 SEQ ID NO: 43 SEQ ID NO: 44 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 45 SEQ ID NO: 46 SEQ ID NO: 41 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 47 SEQ ID NO: 48 SEQ ID NO: 49 SEQ ID NO: 36 SEQ ID NO: 37 SEQ ID NO: 38 SEQ ID NO: 50 SEQ ID NO: 46 [0202] In some embodiments, the first antigen binding domain specifically binds ApoC-II and comprises, or alternatively consists essentially of, or yet further consists of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 comprising, or alternatively consisting essentially of, or yet further consisting of amino acid sequences that are respectively same as amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of 3E4 monoclonal ApoC-II antibody from Thermo Fisher (Catalog No. H00000344-M01, thermofisher.com/antibody/product/APOC2-Antibody-clone-3E4-Monoclonal/H00000344- M01, last accessed April 8, 2024). Alternative sources of ApoC-II antibodies which can be used in the present molecular hooks and methods include: LS Bio (Catalog No. LS-B10603- 0.25, lsbio.com/antibodies/ihc-plus-apoc2-antibody-apolipoprotein-c-ii-antibody-elisa-ihc-ip- wb-western-ls-b10603/295268?trid=247, last accessed April 8, 2024), R&D Systems (Catalog No. AF4497-SP, rndsystems.com/products/human-apolipoprotein-c-ii-apoc2- antibody_af4497, last accessed April 8, 2024), OriGene (Catalog No. TA357157, origene.com/catalog/antibodies/primary-antibodies/ta357157/apolipoprotein-cii-apoc2-rabbit- polyclonal-antibody, last accessed April 8, 2024), and other antibodies listed in Genecards APOC2 page at genecards.org/cgi-bin/carddisp.pl?gene=APOC2, last accessed April 8, 2024). 4906-4947-1849.2 48 Atty. Dkt. No.: 139886-2010 [0203] In some embodiments, the first antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of an scFv, an (scFv)2, an scFvFc, a Fab, a Fab’, a F(ab’)₂, a bispecific antibody or a diabody. In some embodiments, the second antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of an scFv, an (scFv)2, an scFvFc, a Fab, a Fab’, a F(ab’)2, a bispecific antibody or a diabody. [0204] In some embodiments, the molecular hook comprises, or alternatively consists essentially of, or yet further consists of a linker between the first antigen binding domain and the second antigen binding domain, optionally wherein the linker is an enzymatically cleavable linker, a hydrolysable linker, a pH sensitive linker, a photolabile linker, or a self immolative linker. In some embodiments, the linker between the first antigen binding domain and the second antigen binding domain comprises, or alternatively consists essentially of, or yet further consists of a linker from Spycatcher-Spytag system. [0205] In some embodiments, the molecular hook comprises a payload antibody that specifically binds to mutated KRAS. In some embodiments, the KRAS mutation is selected from one or more of G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R, A146T, K117N, or any combination thereof, wherein the wild type KRAS sequence is as shown in SEQ ID NO: 51. Antibodies and antibody fragments that are specific for specific mutant KRAS proteins are known in the art, e.g., as disclosed in US20180086832A1 and US20220177603A1, which are incorporated herein in their entireties. [0206] In some embodiments, the protein specifically binds a KRAS G12V mutant and comprises amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 62 SEQ ID NO: 63 SEQ ID NO: 64 SEQ ID NO: 65 SEQ ID NO: 66 SEQ ID NO: 67 , or a light chain variable region as shown in SEQ ID NO: 60 and a heavy chain variable region as shown in SEQ ID NO: 61. [0207] In some embodiments, the molecular hook is a tetravalent construct that binds to APO-AI and KRAS-G12V mutant. In some embodiments, the molecular hook comprises a heavy chain comprising SEQ ID NO: 68 and a light chain that comprises SEQ ID NO: 69. In some embodiments, the heavy chain comprises an amino acid sequence that is at least 90%, 93%, 95%, 97%, or 99% identical to the sequence as shown in SEQ ID NO: 68. In some 4906-4947-1849.2 49 Atty. Dkt. No.: 139886-2010 embodiments, the heavy chain consists of or consists essentially of an amino acid sequence as shown in SEQ ID NO: 68. In some embodiments, the light chain comprises an amino acid sequence that is at least 90%, 93%, 95%, 97%, or 99% identical to the sequence as shown in SEQ ID NO: 69. In some embodiments, the light chain consists of or consists essentially of an amino acid sequence as shown in SEQ ID NO: 69. [0208] The following examples are included to demonstrate some embodiments of the disclosure. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention. EXAMPLE 1 Experimental Methods Delivering protein into cells using molecular hooks [0209] The presently disclosed molecular hooks allow large molecules (macromolecules) such as peptides, proteins, or antibodies (all types of antibodies: IgA, dimeric IgA, IgD, IgE, IgG1, IgG2, IgG3, IgG4, IgM), and all types of antibody fragments, to be delivered inside the cell, bioactively, without being trapped by the endosomal trap. Antibody fragments that can be delivered using the disclosed molecular hooks include, but are not limited to, Fv (Fragment Variable), Fc (Fragment Crystallizable) (antibody tail region), Fab (Fragment antigen-binding, consists of one constant and one variable domain of both light and heavy chains), Fab' (Fab with part of the hinge), (Fab')2 (two Fab regions with hinge), scFv (single- chain Fragment Variable) (VL and VH fragment), di-scFv (sometimes referred to as dscFv or diabody) (divalent scFv, two scFv fragments linked), tri-scFv (triabody) (three scFv fragments linked), scFab (Single-chain Fab) (Fab element, connected by a linker instead of a hinge), minibody antibody (two scFv fragments linked to two CH3 regions), scFv-Fc (two scFv fragments linked to the Fc region, but around 50 kDa lighter than a full-size IgG), and MANAbodies (as described in Skora, Andrew D., et al. "Generation of MANAbodies specific to HLA-restricted epitopes encoded by somatically mutated genes." Proceedings of the National Academy of Sciences 112.32 (2015): 9967-9972, incorporated herein in its entirety). [0210] The present molecular hooks are designed to have two parts. The first part encompasses a domain that binds to proteins carried by natural or artificially produced lipid 4906-4947-1849.2 50 Atty. Dkt. No.: 139886-2010 nanoparticles, e.g., HDL molecules. These proteins include Apolipoprotein A-I, Apolipoprotein A-IV, Apolipoprotein L1, Apolipoprotein C-III, Apolipoprotein E, Apolipoprotein A-II, Apolipoprotein C-I, Alpha-1-antitrypsin, Apolipoprotein C-II, Apolipoprotein M, Alpha-2-HS-glycoprotein, Complement C3, Serum Amyloid A4, and Apolipoprotein B. [0211] The second part of the molecular hooks specifically binds a protein (“payload”) to be transferred into a cell. In some embodiments, the payload is an antibody. In some embodiments, the payload is an antibody that specifically binds mutated signaling proteins most commonly found in cancer patients, such as KRAS mutations, but not the wild-type signaling proteins normally found in individuals without cancer. [0212] Mutations in the KRAS gene are particularly well known in cancer biology and are one of the most common mutations in many different types of cancer. KRAS mutations cause uncontrolled cell proliferation by affecting the RAS-RAF-MEK-ERK pathway, which is indispensable for the survival and proliferation of cells. The most common KRAS mutations occur specifically at codons 12, 13, and 61. Blocking specifically mutated KRAS provides definitive results in cancer treatment unless there is a different mutation in the RAS-RAF- MEK-ERK pathway. In particular, some mutant forms of KRAS (e.g., G12C) have become the focus of targeted therapy. [0213] The most common KRAS mutations are as follows: 1. Mutations in codon 12 are the most common mutations in the KRAS gene and are found in many types of cancer (especially in colon, lung, and pancreatic cancers). G12D (Glycine → Aspartic Acid), G12V (Glycine → Valine), G12C (Glycine → Cysteine), G12A (Glycine → Alanine), G12S (Glycine → Serine) and G12R (Glycine → Arginine); 2. Mutations in codon 13 are also significant and are often found in colon cancer. G13D (Glycine → Aspartic Acid); 3. Mutations in codon 61 involve the substitution of different amino acids in place of glycine and may be present in other types of cancer. Q61H (Glutamine → Histidine), Q61L (Glutamine → Leucine), Q61R (Glutamine → Arginine); and 4. Less common mutations in KRAS have also been identified in some types of cancer: A146T (Alanine → Threonine): Found especially in colon cancer and K117N (Lysine → Asparagine). [0214] In some embodiments, the protein specifically binds a KRAS G12V mutant and comprises amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 4906-4947-1849.2 51 Atty. Dkt. No.: 139886-2010 SEQ ID NO: 62 SEQ ID NO: 63 SEQ ID NO: 64 SEQ ID NO: 65 SEQ ID NO: 66 SEQ ID NO: 67 , or a light chain variable region as shown in SEQ ID NO: 60 and a heavy chain variable region as shown in SEQ ID NO: 61. [0215] In some embodiments, the heavy chain comprises an amino acid sequence that is at least 90%, 93%, 95%, 97%, or 99% identical to the sequence as shown in SEQ ID NO: 68. In some embodiments, the heavy chain comprises an amino acid sequence as shown in SEQ ID NO: 68. In some embodiments, the light chain comprises an amino acid sequence that is at least 90%, 93%, 95%, 97%, or 99% identical to the sequence as shown in SEQ ID NO: 69. In some embodiments, the light chain comprises an amino acid sequence as shown in SEQ ID NO: 69. [0216] In summary, the molecular hook constructs of the present disclosure bind to two distinct antigens. One arm of the construct targets a protein associated with high-density lipoprotein (HDL), the body's natural lipid nanoparticle. This enables the construct to enter the cell via HDL-mediated delivery. In some embodiments, the other arm of the molecular hook is designed to bind to a mutated signaling protein within the cell that drives oncogenic processes. Once inside the cell, the second arm of the molecular hook targets and inhibits autonomous signaling proteins involved in cell proliferation, such as mutated KRAS, thereby halting uncontrolled cell growth. [0217] Materials and Methods: Human serum containing naturally occurring ApoA1 and human nanolipid (HDL) particles are added at a concentration of 10%. HepG2 cell line used (DSMZ no. ACC180) was obtained from the Leibniz Institute (DSMZ Human and Animal Cell Line Department). [0218] HepG2 cells, as mentioned earlier, are cultured in 75 cm² cell culture flasks containing 15 ml Eagle's Minimal Essential Medium (MEM) supplemented with 10% human serum Type AB (Capricon Scientific Cat-No: HUM-3B), penicillin/streptomycin (Capricon Scientific Cat-No: PS-B). [0219] To validate the concept, an antibody against mutant KRAS is used as the payload to be transported into the liver cells. [0220] Preparation of bacterial cultures in LB medium: Mix 10g Tryptone (Sigma-Aldrich, USA®), 5g yeast extract, and 10g NaCl (Sigma-Aldrich, USA) in a conical flask, and add 4906-4947-1849.2 52 Atty. Dkt. No.: 139886-2010 950 ml autoclaved distilled water (pH 7.0). Autoclave the mixture at 15 psi for 20 minutes. After autoclaving and cooling, add antibiotics (ampicillin). The transformed bacteria adapted in the previous step are subjected to mini culture in an antibiotic medium. The bacteria cultured overnight at 1200 rpm and 37°C are centrifuged at the end of the culture. [0221] The isolation of plasmid DNA from bacterial pellets is performed using the NucleoSpin Plasmid Miniprep Kit (MACHEREY-NAGEL GmbH & Co. KG). The concentration of plasmids and the A260/A280 ratios are measured spectrophotometrically. [0222] Preparation of functional molecular hooks. Antibodies are bound to each other via the Fc portion in a bispecific manner. For this purpose, two biomacromolecules that can simultaneously bind two separate epitopes, sold under the name “SpyCatcher” and “SpyTag,” were used. This enables the unique biological effects that neither a single antibody nor two unbound antibodies could achieve alone by linking the two antibodies to each other. Two ready-to-use immunoglobulin G (IgG) antibodies were assembled. The process proceeded as follows: Both workflows can be summarized in two steps: Anti-ApoA1, a photoreactive peptide called "SpyCatcher," also a photo-reactive peptide called "SpyTag," were combined under 365 nm light. Subsequently, the two antibodies were assembled through spontaneous isopeptide bond formation between SpyTag and SpyCatcher (as described in Mei, L.et al. (2021). Rapid production of bispecific antibodies from off-the-shelf IgGs with high yield and purity. Bioconjugate chemistry, 33(1), 134-141, incorporated herein in its entirety). [0223] Preparation of two chain tetravalent molecular hooks. Applicant also produced tetravalent bispecific molecular hooks that comprise two polypeptide chains: a heavy chain and a light chain. The heavy chain is engineered to include three tandem variable domains and constant regions arranged as follows: VH1–CH1–CH2–(GGGGS)₃–VH2–(GGGGS)₃– VL2–VL1–CL1. This configuration enables multivalent binding capacity and structural flexibility. The heavy chain comprised SEQ ID NO: 68 and the light chain comprised SEQ ID NO: 69. [0224] In vitro transfection of proteins (profection) using molecular hooks. Molecular hooks that are loaded with a payload protein are incubated with HDL molecules, where the molecular hook binds to a protein on the HDL, forming an HDL-molecular hook complex. Target cells are incubated with the HDL-molecular hook complexes. The cells are cultured in 75 cm² cell culture flasks containing 15 ml Eagle's Minimal Essential Medium (MEM) supplemented with 10% human serum Type AB (Capricon Scientific™ Cat-No: HUM-3B) 4906-4947-1849.2 53 Atty. Dkt. No.: 139886-2010 and penicillin/streptomycin (Capricon Scientific™ Cat-No: PS-B) in an atmosphere of 95% air and 5% CO2 at 37°C. [0225] Following profection, the efficiency of intracellular payload protein delivery is measured by a protein detection method (western blot or flow cytometry) at different time points (e.g., 2, 4, 6, 8, 12, 24, 48, 72 hours, or any value therebetween). [0226] In some embodiments, the payload protein disturbs a signaling process in the cell. In some embodiments, the payload protein is an antibody, or an antigen binding fragment thereof, that binds and inhibits a mutated signaling protein in the cell. In these instances, the downstream signaling effects (such as a target phosphorylation or lack thereof) can be used as a surrogate readout of profection efficiency. In a specific embodiment, the payload protein (anti-mutated KRAS antibody) disrupts mutated KRAS signaling, and phospho-MAPK (anti phospho-ERK1/2, anti-phospho-MEK1/2 etc.) western blots can be used to monitor effective delivery of anti-mutated KRAS antibodies. [0227] In vivo profection using molecular hooks. Molecular hooks that are loaded with a payload protein are administered to the bloodstream of a subject, where the molecular hooks bind to circulating HDL molecules, forming an HDL-molecular hook complex. In some embodiments, molecular hooks are loaded on to HDL molecules ex vivo and administered as a pre-formed HDL-molecular hook complex. [0228] Following profection, the efficiency of intracellular payload protein delivery is measured by a protein detection method (western blot or flow cytometry) at different time points (e.g., 2, 4, 6, 8, 12, 24, 48, 72 hours, or any value therebetween). [0229] In some embodiments, the payload protein disturbs a signaling process in the cell. In some embodiments, the payload protein is an antibody, or an antigen binding fragment thereof, that binds and inhibits a mutated signaling protein in the cell. In these instances, the downstream signaling effects (such as a target phosphorylation or lack thereof) can be used as a surrogate readout of profection efficiency. In a specific embodiment, the payload protein (anti-mutated KRAS antibody) disrupts mutated KRAS signaling, and phospho-MAPK (anti phospho-ERK1/2, anti-phospho-MEK1/2 etc.) western blots can be used to monitor effective delivery of anti-mutated KRAS antibodies. Example 2: Testing Delivery of Molecular hooks into cells [0230] A study was conducted to evaluate the ability of HDL particles to deliver macromolecules—specifically, rabbit-derived anti-ApoA1 antibodies—into cells. For this 4906-4947-1849.2 54 Atty. Dkt. No.: 139886-2010 purpose, the human pancreatic cancer cell line PANC-1 was utilized as the in vitro model system. The results demonstrated successful intracellular delivery of the antibodies via HDL- mediated transport. [0231] The aim of the study was to assess the fluorescence intensity deriving from internalization of dye-conjugated ApoA-I antibody that is used in molecular hooks of the present disclosure. Increase of cell fluorescence indicates internalization, as the intracellular acidic conditions release the dye from the antibody, causing the rise in fluorescence. Increase of background fluorescence indicates acidification of the cell culture medium. PANC1 pancreatic cancer cell line was used in the tests comparing internalization of conjugated ApoA-I antibody and anti-HEL IgG as isotype control. PANC-1 cells are human pancreatic ductal adenocarcinoma cell line, registered under ATCC number ATCC-CRL-1469. Although PANC-1 cells were utilized in this proof-of-concept study, the HDL-based delivery system is broadly applicable to all human cell types. This claim is grounded in the inherent biocompatibility and universal presence of HDL receptors across diverse human tissues, supporting the potential for widespread intracellular transport of macromolecules via this mechanism. In Example 4, Applicant provides additional data that molecular hooks of the present disclosure can deliver cargo (e.g., therapeutic antibodies) into genetically distinct cells. [0232] The rationale for selecting this specific antibody lies in its affinity for HDL, a naturally occurring lipid nanoparticle endogenous to the human body. The intended outcome was to demonstrate that, when conjugated to HDL, the antibody could be effectively internalized by target cells. This approach supports the concept of utilizing HDL as a biocompatible carrier for intracellular delivery of therapeutic macromolecules. [0233] For this purpose, two distinct classes of antibodies were selected. The first is a rabbit- derived IgG antibody targeting the ApoA1 antigen, which is naturally present on HDL particles. The second is a rabbit-derived anti-HEL IgG antibody developed against hen egg lysozyme (HEL), an antigen that is neither present on HDL particles nor associated with any human proteins—thus serving as a non-specific control. Henceforth, within the scope of the present patent application, the anti-ApoA1 IgG antibodies will be referred to as Compound- A, and the anti-HEL IgG antibodies will be designated as HEL. Each antibody was individually conjugated with PhAb, a fluorescent dye that enables visualization and quantification of cellular internalization through flow cytometry and fluorescence-based imaging techniques. 4906-4947-1849.2 55 Atty. Dkt. No.: 139886-2010 Reagent conjugation with dye [0234] 2x100 ug antibody conjugation with pHAb Amine Reactive Dye was carried out as follows: 80 ug of both Compound A and aHEL IgG1 isotype control was conjugated with 20:1 molar excess of pHAb Reactive Dye. Dye was dissolved in 1:1 DMSO-water mixture and conjugation was carried out for compound A and aHEL IgG1 isotype control antibody. Conjugation mixture was incubated at ambient temperature for 60 min using rotary mixer protected from light. Free label was then removed and antibody was buffer exchanged to PBS, pH 7.4 using desalt column twice. Conjugated antibody concentration and DAR was calculated using manufacturer's instructions. As a result, 55 ug of Compound A at 0.8 mg/mL and 54 ug anti-HEL IgG1 antibody conjugated to pHAb Reactive Dye were recovered from this experiment. The DAR values were 2.9 and 2.7, respectively. Labelled and untreated samples were loaded on SDS-PAGE to check for aggregation. Results [0235] Initially, PANC1 cells were incubated for 48h in presence or absence of 50ug/ml conjugated ApoA-I antibody or anti-HEL-pHAb (isotype control) in cell culture media containing 10% normal human serum. Cells were released from tissue culture wells with 5mM EDTA/PBS solution, 10 minutes at 37C. The cells were then spun down and suspended into FACS buffer for analysis with Beckmann Coulter CytoFlex flow cytometer. For each condition, 10000 events were recorded and live cells were gated out. Live cell populations are shown in FIGS 2A-2B. [0236] Surprisingly, more than 71% of cells internalized the conjugated antibody as compared to an isotype antibody control (FIG.2A), and more than 97% internalized as compared to an untreated control (FIG.2B). This showed that molecular hooks can efficiently be delivered to target cells on HDL molecules. [0237] Time course study. PANC1 cells were incubated for 24, 48 or 96 hours in presence or absence of 50ug/ml conjugated ApoA-I antibody or anti-HEL-pHAb (isotype control) in cell culture media containing 10% normal human serum. As a positive control, PANC1 cells were incubated for 48 hours in the presence of conjugated ApoA-I antibody or anti- HEL- pHAb (isotype control) and PEI. Cells were released from tissue culture wells with 5mM EDTA/PBS solution, 10 minutes at 37C. The cells were then spun down and suspended into FACS buffer for analysis with Beckmann Coulter CytoFlex flow cytometer. For each condition, 10000 events were recorded and live cells were gated out. 4906-4947-1849.2 56 Atty. Dkt. No.: 139886-2010 [0238] FIG.2C shows that internalization of the conjugated ApoA-I antibody increases over time and is durable until 96 hours (almost 70% internalization). The HEL–pHAb antibody used as a negative control exhibited minimal cellular uptake—only 1.15% at 48 hours and 1.09% at 96 hours—demonstrating no significant internalization. In contrast, the conjugated ApoA-I antibody, which constitutes the delivery vehicle for mRNA in COMED’s Molecular Hook system, demonstrated substantially higher intracellular uptake: 50.7% at 48 hours and 67.3% at 96 hours (FIG.2C, FIG.2D). These findings clearly indicate that COMED’s Molecular Hook technology enables efficient and progressive cellular internalization of the antibody conjugate over time. [0239] A control experiment showed that anti-HEL antibodies (which do not target HDL molecules) are not internalized over the same time course (FIG.2E). Molecular Hook Antibodies are not Trapped in Endosomes once Internalized. [0240] One potential pitfall of cell internalization is endosomal entrapment. If an internalized antibody is trapped in an endosome, it is not available to bind its target and is eventually degraded. In other words, an antibody in an endosome is therapeutically useless, even though it is internalized into the cell. [0241] pHAb is a fluorescent dye that binds to antibodies and is ideally suited for detecting antibodies that have been internalized by the cell. Since the pHAb dye is sensitive to intracellular pH, it emits fluorescence depending on whether the internalized antibody has undergone lysosomal degradation: a strong fluorescent signal is observed when the antibody is trapped in lysosomes. A weak signal is observed when the antibody remains in the cytoplasm, indicating successful evasion of lysosomal entrapment. [0242] Applicant conducted imaging experiments (in combination with FACS) using pHAb and showed that the internalized antibody is not trapped in endosomes, but is readily available in the cell cytoplasm even after 93 hours (FIGS.3A-3B). [0243] These experiments show that the disclosed molecular hooks can effectively internalize into target cells via HDL-mediated delivery and are able to deliver their load into the cytoplasm. The signal is still detectable 24 hours post-treatment, indicating intracellular persistence of the compound. The pHAb signal is mild, suggesting the compound has avoided lysosomal entrapment and is likely localized within the cytoplasm rather than degraded. Molecular hooks’ ability to avoid endosomal traps is important for their efficacy. 4906-4947-1849.2 57 Atty. Dkt. No.: 139886-2010 The uptake rate within the first 24 hours is quantified as 48.8%, demonstrating efficient internalization. Example 3: Molecular Hooks can specifically target mutant proteins in cell [0244] Beyond mere internalization, Applicant further demonstrated the intracellular functionality of the molecular hook—a tetravalent bispecific antibody (intrabody)—following successful entry into the cell. This functional activity is critical, as it confirms that the intrabody remains intact and operational within the cytosolic environment, rather than undergoing degradation in endolysosomal compartments. Accordingly, the molecular hook is capable of executing its intended intracellular task, such as target engagement or pathway modulation, thereby validating its role as an effective therapeutic or diagnostic agent. [0245] To achieve the intended intracellular delivery and functional targeting, the molecular hook was designed as a tetravalent bispecific antibody construct. One arm of the construct comprises a variable region capable of binding to antigen ApoA1, which is associated with HDL particles, thereby enabling the molecular hook to attach to HDL and co-travel through the circulatory and interstitial compartments. The opposing arm consists of a variable region derived from a second antibody (war-head), specifically engineered to recognize and bind a defined mutated intracellular signaling protein like as KRAS G12V. Upon cellular internalization, this arm facilitates functional blockade of the target protein, thereby exerting the desired biological effect. [0246] To evaluate the target specificity of the molecular hook, a Biolayer Interferometry (BLI) analysis was performed. The intrabody component of the construct was designed to selectively bind mutant intracellular signaling proteins—such as KRAS G12V—while exhibiting minimal or no affinity toward the corresponding wild-type isoforms. This assessment was critical to confirm that the molecular warhead of the construct retains mutation-specific binding characteristics, thereby ensuring functional precision and minimizing off-target interactions within healthy cells. BLI analysis [0247] Biolayer Interferometry (BLI) measures the interactions between two or more biomolecules by analyzing interference patterns of white light reflected from the surface of a biosensor tip. During kinetic analysis, a biomolecule of interest is immobilized onto a biosensor surface (ligand). A titration series of interacting biomolecule in solution (analyte) is introduced to the sensor surface. Changes in light wave interference, which occur when 4906-4947-1849.2 58 Atty. Dkt. No.: 139886-2010 molecules associate or dissociate from a sensor surface, are recorded in time and results are plotted as sensorgrams. A sensorgram is a plot that shows how the response of a biosensor changes over time as molecules interact on the sensor surface. The vertical axis usually represents the sensor signal (such as resonance units in SPR, or optical/electrical response in other biosensors), while the horizontal axis represents time. [0248] The aim of the study was to determine the kinetic parameters of the molecular hook against mutant KRAS (KRAS G12V). Materials and methods [0249] Materials used: Tetravalent molecular hook that binds HDL and mutant KRAS (KRAS G12V), 191 kDa, 1 mg/mL; • KRAS G12V protein (Compound-G), 23 kDa, His-tag, 0.6 mg/mL; KRAS WT protein (Compound-Control), 23 kDa, His-tag, 0.6 mg/mL. [0250] Instrument: Sartorius Octet Red96e equipped with ProG (Protein G, Lot: 2408018011) and Ni-NTA (Nickel-charged tris-NTA, Lot: 2409008411) sensors. The data was analyzed with Octet Analysis Studio version 13.0.3.52. [0251] Assay design for kinetics of molecular-hook: Octet ProG sensors were used in baseline 1 measurement for 60 sec. Molecular Hook (COM0003-A01_FIN1), diluted to 10 μg/mL using kinetic buffer, was loaded onto the sensors for 120 sec. For baseline 2 measurement, sensors were transferred to kinetic buffer for 60 sec. In the association (ka) step, the sensors were measured in a Compound-G concentration gradient of 500 nM – 7.8 nM (2x serial dilutions, 7 dilutions in total). In addition, sensors were transferred to kinetic buffer for off-rate (kd) measurement for 7200 sec. A baseline reference sensor (0 nM, Compound-G) was also included in the assay. [0252] Sample deck temperature was set to 30 °C as suggested by Sartorius, which translates to a binding interaction temperature of approximately 25 °C. The obtained data was referenced using the baseline reference sensors, followed by Y-aligning to the average of baseline 2 step. Inter-step (bulk shift) correction was set to the beginning of the dissociation step. The Savitzky-Golay filter was employed to reduce the level of noise of the obtained sensorgrams. The sensorgrams were fitted for ka and kd using the 1:1 global binding model. Results [0253] Sensorgram of KRAS G12V (Compound-G) binding to immobilized molecular hook comprising KRAS G12V antibody (COM0003-A01-FIN1) is as shown in FIG.5A. The 4906-4947-1849.2 59 Atty. Dkt. No.: 139886-2010 results show that the molecular hook displays specific and strong affinity towards target molecule (KRASG12V mutant protein), which is mainly attributed to a slow off-rate. Fit quality is good. [0254] In contrast, the molecular hooks did not show any affinity towards wild type KRAS at any concentration tested (FIG.5B). [0255] The molecular hook that targets HDL and mutant KRAS exhibited no detectable binding activity toward the wild-type (unmutated) KRAS signaling protein. In contrast, the same construct demonstrated high-affinity and selective interaction with the oncogenic KRAS G12V mutant, thereby confirming its mutation-specific targeting capability. [0256] The molecular hook design of the present disclosure offers a novel approach to intracellular targeting of disease-relevant macromolecules by enabling selective delivery and functional engagement via HDL-mediated transport. [0257] One of the key advantages lies in the construct’s ability to discriminate between mutant and wild-type intracellular signaling proteins. Specifically, the molecular hook demonstrates high-affinity binding to the oncogenic KRAS G12V mutant, while exhibiting no detectable activity against the wild-type KRAS isoform. [0258] This mutation-specific targeting is critical, as KRAS is an essential cytosolic protein required for normal cellular viability. Inhibition of wild-type KRAS would result in non- selective cytotoxicity, rendering the molecule therapeutically unsafe. [0259] By contrast, the molecular hook’s selective inhibition of mutant KRAS G12V enables targeted elimination of cancer cells without harming healthy tissue. This specificity transforms KRAS—historically classified as an “undruggable” target due to its intracellular localization and structural constraints—into a “druggable” entity. Accordingly, the molecular hook provides a viable therapeutic strategy for addressing previously inaccessible oncogenic drivers, thereby expanding the scope of intracellular antibody-based interventions. Similarly, other intracellular “undruggable” targets can be targeted by the presently disclosed molecular hook design. Example 4: Molecular Hooks can deliver cargo to various cell lines [0260] The same experimental procedures conducted on PANC1 cells were also performed on MIA-PaCa-2 and CAPAN-2 cell lines, yielding consistent and mutually corroborative results. MIA-PaCa-2 is an epithelial cell line derived from the pancreas of a 65-year-old 4906-4947-1849.2 60 Atty. Dkt. No.: 139886-2010 White male diagnosed with carcinoma. This cell line is suitable for use in ISO 17025- accredited laboratories for assay validation, method comparison, and performance testing, including assessments of sensitivity, linearity, and specificity. CAPAN-2, characterized by its polygonal morphology, was isolated in 1975 from the pancreas of a 56-year-old White male patient with pancreatic adenocarcinoma. [0261] A key distinction among the three pancreatic cancer cell lines—PANC1, MIA-PaCa- 2, and CAPAN-2—lies in their respective oncogenic mutation profiles. PANC1 cells harbor the KRAS G12D mutation and exhibit additional mutations in TP53, CDKN2A, and SMAD4, which are commonly associated with impaired cell cycle regulation and tumor suppressor function. MIA-PaCa-2 cells carry the KRAS G12C mutation and also present mutations in TP53, CDKN2A, and PTEN, contributing to disrupted apoptotic signaling and enhanced proliferative capacity. CAPAN-2 cells possess the KRAS G12V mutation and are characterized by mutations in TP53 and BRCA2, the latter of which is linked to DNA repair deficiencies and genomic instability. [0262] These distinct mutational landscapes influence intracellular signaling pathways, cellular uptake mechanisms, and therapeutic responsiveness. The reproducibility of COMED- Hook 02 internalization across these genetically diverse models reinforces the robustness and broad applicability of the claimed invention. [0263] Moreover, cells harboring these oncogenic mutations—including KRAS G12D, G12C, and G12V—are not limited to pancreatic carcinomas. They are also commonly found in non-small cell lung cancers, colorectal cancers, biliary tract malignancies, gastric cancers, and certain endometrial and ovarian tumors. The presence of these mutations across multiple tumor types underscores the broader relevance of the presently disclosed molecular hook delivery platform and supports its potential applicability beyond pancreatic cancer models. The successful internalization observed in these representative cell lines suggests broader translational potential, indicating that similar delivery efficiency may be achievable in other cancer cell types or even in normal healthy cells exhibiting comparable molecular characteristics. [0264] Significant internalization findings were similarly observed in other cell types. One such example is the MIA-PaCa-2 cell line, previously referenced above. In the following section, we present a representative dataset demonstrating that internalization is 4906-4947-1849.2 61 Atty. Dkt. No.: 139886-2010 concentration-dependent, further supporting the mechanistic consistency of molecular hook approach across varying experimental conditions. [0265] MIA-PaCa-2 cells were exposed to molecular hooks at final concentrations of 4.4, 13.3, and 40 μg/ml. Under these conditions, the cells successfully internalized the molecular hook at rates of 4.32%, 29.3%, and 82.5%, respectively (FIG.6A). These findings demonstrate a clear concentration-dependent internalization profile, further supporting the efficacy and scalability of the molecular hook platform in genetically distinct pancreatic cancer models. [0266] A specificity assessment was conducted using the MIA-PaCa-2 cell line. In addition to exposure to the molecular hook, cells were treated with anti-HEL rabbit IgG antibodies alone and with PEI-complexed anti-HEL antibodies, all at a final concentration of 13.3 μg/mL. Under these conditions, the molecular hook achieved an internalization rate of 29.3%, whereas the negative control—anti-HEL rabbit IgG antibodies—showed only 6.76% internalization (FIG.6B). The positive control, consisting of PEI-complexed anti-HEL antibodies, yielded 15.3% internalization. These results confirm the specificity and functionality of the assay, demonstrating that molecular hook facilitates targeted and efficient cellular uptake beyond nonspecific or PEI-assisted delivery mechanisms. [0267] MIA-PaCa-2 cells (KRAS G12C; TP53 R248W) represent a metabolically aggressive subtype of pancreatic ductal adenocarcinoma (PDAC), capable of acquiring alternative fuel sources under nutrient-deprived conditions via macropinocytosis and SR-B1-mediated HDL- lipid uptake. Upon exposure to EIPA, a macropinocytosis inhibitor, these cells demonstrated a compensatory increase in SR-B1-mediated uptake, resulting in enhanced internalization of the molecular hook. This shift in uptake mechanism provides compelling evidence for the adaptability and robustness of the molecular hook delivery platform under dynamic metabolic constraints. [0268] At a concentration of 13.3 μg/ml, MIA-PaCa-2 cells internalized molecular hook at a rate of 29.3% by the 96-hour time point (FIG.6C). However, upon the addition of EIPA (5- (N-ethyl-N-isopropyl)amiloride), a macropinocytosis inhibitor, the cells were deprived of one of their primary nutrient acquisition pathways. In response, they appeared to shift entirely toward SR-B1-mediated HDL uptake, resulting in a marked increase in molecular hook internalization to 83% (FIG.6C). This dramatic increase strongly suggests a compensatory 4906-4947-1849.2 62 Atty. Dkt. No.: 139886-2010 shift toward SR-B1-mediated uptake, reinforcing the versatility and adaptability of the molecular hook platform under dynamic metabolic constraints. [0269] This finding not only validates the multi-pathway entry mechanism proposed in this disclosure, but also highlights its potential to exploit tumor-specific metabolic vulnerabilities. The ability of the molecular hook to achieve enhanced internalization in response to pathway inhibition underscores its robustness and therapeutic promise. [0270] Such a result may be viewed as emblematic of the broader impact this invention could have in oncology—offering a delivery strategy that is not only targeted and efficient but also responsive to the metabolic landscape of cancer cells. CAPAN-2 Cell Line Experiments [0271] The present disclosure is directed to intracellular delivery of cargos—including peptides, polypeptides/proteins, enzymes, and/or antibodies—via a molecular hook comprising a tetravalent, bispecific antibody pair configured to bind endogenous natural lipid nanoparticles of human origin, in particular high-density lipoprotein (HDL) particles. In certain embodiments, the molecular hook is configured to engage HDL particles and chaperone the cargo into target cells. In other embodiments, the cargo is selected from at least one of: a peptide, a polypeptide/protein, an enzyme, and/or an antibody. By way of example and without limitation, the molecular hook has been evaluated in the CAPAN-2 human pancreatic ductal adenocarcinoma (PDAC) cell line. [0272] Without wishing to be bound by theory, PDAC cells sustain growth under nutrient limitation by engaging macropinocytosis of extracellular macromolecules and by SR-B1 (SCARB1)–mediated uptake of HDL-associated lipids. The dual-entry design of the molecular hook is intended to leverage these complementary uptake routes to achieve robust intracellular access across variable microenvironmental conditions. In certain embodiments, the hook’s effector (“warhead”) is configured to bind and/or functionally inhibit mutant KRAS (e.g., KRAS G12V) once intracellularly delivered. [0273] CAPAN-2 Evaluation. CAPAN-2 cells were exposed to 40 µg/mL of the molecular hook and assessed at the 48-hour time point. Under basal conditions, intracellular uptake reached 46.9%. Upon addition of EIPA (a macropinocytosis inhibitor), uptake decreased to 14.1%. These data indicate that macropinocytosis constitutes a dominant entry route for the molecular hook in CAPAN-2 cells; when this route is pharmacologically constrained, the 4906-4947-1849.2 63 Atty. Dkt. No.: 139886-2010 cells exhibit a compensatory bias toward SR-B1–mediated HDL uptake, which—while detectable—does not fully restore the basal uptake level. [0274] Advantages. Collectively, these findings (i) validate the dual-entry architecture (macropinocytosis and SR-B1) of the molecular hook; (ii) support targeting of intracellular oncogenic KRAS (e.g., KRAS G12V) by the molecular hook’s warhead (e.g., therapeutic antibody) after cytosolic access is achieved; and (iii) demonstrate a delivery advantage under conditions in which macropinocytosis is inhibited, with SR-B1–mediated uptake providing a compensatory, fail-safe pathway that enhances the robustness of intracellular delivery in PDAC models. [0275] CAPAN-2 cells were exposed to molecular hook at final concentrations of 4.4, 13.3, and 40 μg/ml. Under these conditions, the cells successfully internalized COMED-Hook 02 at rates of 1.82%, 7.01%, and 46.9%, respectively (FIG.7A). These findings demonstrate a clear concentration-dependent internalization profile, further supporting the efficacy and scalability of the molecular hook platform in genetically distinct pancreatic cancer models. [0276] A specificity assessment was conducted using the CAPAN-2 cell line. In addition to exposure to molecular hook, cells were treated with anti-HEL rabbit IgG antibodies alone and with PEI-complexed anti-HEL antibodies, all at a final concentration of 40 μg/ml. Under these conditions, COMED-Hook 02 achieved an internalization rate of 46.9%, whereas the negative control—anti-HEL rabbit IgG antibodies—showed only 12.1% internalization (FIG. 7B). The positive control, consisting of PEI-complexed anti-HEL antibodies, yielded 19.9% internalization. These results confirm the specificity and functionality of the assay, demonstrating that molecular hook facilitates targeted and efficient cellular uptake beyond nonspecific or PEI-assisted delivery mechanisms. [0277] At a concentration of 40 μg/mL, CAPAN-2 cells internalized COMED-Hook 02 at a rate of 46.9% by the 48-hour time point. Upon the addition of EIPA, a macropinocytosis inhibitor, the cells were deprived of one of their primary nutrient acquisition pathways. In response, they appeared to shift toward SR-B1-mediated HDL uptake. However, unable to utilize macropinocytosis for further internalization, the uptake rate of COMED-Hook 02 dropped significantly to 14.1%. See FIG.7C. Molecular Hooks are Functional Once inside the Cell 4906-4947-1849.2 64 Atty. Dkt. No.: 139886-2010 [0278] CAPAN-2 cells comprise a KRAS G12V mutation. Applicant tested whether molecular hooks carrying a anti-KRAS G12V specific therapeutic antibody are functional after [0279] Phase-contrast microscopy of CAPAN-2 cultures treated with the non-target control (anti-HEL) antibody showed no overt cytotoxicity or cytostasis up to 96 hours, with cells remaining adherent and proliferative despite modest vacuolization consistent with culture- related stress (FIG.8A). In contrast, phase-contrast imaging of CAPAN-2 cultures treated with COMED-Hook 02 demonstrated a time-dependent transition from cytostasis to cytotoxicity (24→96 h), evidenced by reduced expansion of the monolayer, increased vacuolization, phase-bright rounding and partial detachment, in contrast to the non-target control (FIG.8B). [0280] These results confirmed that the molecular hook not only facilitates intracellular delivery of the therapeutic antibody but also preserves its functional integrity, resulting in a pronounced biological effect upon internalization. Example 5: Outcomes Following Intracellular KRAS G12V Neutralization via COMED’s Molecular Hook [0281] Without wishing to be bound by a particular theory, oncogenic KRAS G12V maintains a sustained Ras-GTP state that elevates macropinocytic flux through coordinated activation of RAF–MEK–ERK and PI3K–AKT–mTOR pathways, together with RAC1/PAK- dependent actin remodeling and NHE1-dependent membrane ruffling and cup closure. In certain embodiments, intracellular delivery of the molecular hook carrying a warhead (e.g., an antibody) against the KRAS G12V mutant protein to CAPAN-2 (KRAS G12V) cells results in functional inhibition of KRAS G12V, which produces the following outcomes: [0282] Acute suppression of macropinocytosis. Reduced formation/closure of macropinocytic cups and decreased uptake of high-molecular-weight tracers (e.g., albumin, dextran), leading to diminished lysosomal proteolysis of extracellular proteins and a lower intracellular amino-acid pool. [0283] Attenuation of growth signaling and protein synthesis. Downstream decreases in pERK and pAKT with consequent reduction of mTORC1 activity (e.g., reduced pS6K/p4E- BP1), accompanied by AMPK activation and an integrated stress response (e.g., ATF4 induction) under nutrient-limited conditions. 4906-4947-1849.2 65 Atty. Dkt. No.: 139886-2010 [0284] Compensatory shift to lipid import. A relative increase in reliance on SR-B1– mediated HDL uptake to support membrane biogenesis and energy homeostasis. In certain embodiments, this shift biases intracellular delivery of molecular hook toward the SR-B1 entry route, thereby maintaining (or restoring) cytosolic exposure of the anti-KRAS G12V antibody even as macropinocytosis is dampened. [0285] Functional vulnerabilities and anti-proliferative effects. Under low-nutrient or albumin-poor conditions, concurrent loss of macropinocytic amino-acid supply and reduced mTORC1 signaling is expected to yield cell-cycle arrest and/or apoptosis. In some embodiments, KRAS G12V neutralization synergizes with pharmacologic macropinocytosis inhibitors (e.g., EIPA) or with agents that limit extracellular protein availability, producing enhanced cytotoxicity in PDAC models. List of Sequences [0286] SEQ ID NO: 1, CDR-L1 of an APOA-II antibody, Artificial sequence RSSKSLLYKDGKTYLN [0287] SEQ ID NO: 2, CDR-L2 of an APOA-II antibody, Artificial sequence LMSTRAS [0288] SEQ ID NO: 3, CDR-L3 of an APOA-II antibody, Artificial sequence QQLVEYPLT [0289] SEQ ID NO: 4, CDR-H1 of an APOA-II antibody, Artificial sequence GYTFTNYWMH [0290] SEQ ID NO: 5, CDR-H2 of an APOA-II antibody, Artificial sequence NIYPGSGNTNYNEKFK [0291] SEQ ID NO: 6, CDR-H3 of an APOA-II antibody, Artificial sequence RYGYVDWFAY [0292] SEQ ID NO: 7, CDR-L1 of an APOA-II antibody, Artificial sequence RASQDTSNYLN [0293] SEQ ID NO: 8, CDR-L2 of an APOA-II antibody, Artificial sequence YTSRLHS [0294] SEQ ID NO: 9, CDR-L3 of an APOA-II antibody, Artificial sequence QQGNTLPYT [0295] SEQ ID NO: 10, CDR-H1 of an APOA-II antibody, Artificial sequence GYTFTSYWMH 4906-4947-1849.2 66 Atty. Dkt. No.: 139886-2010 [0296] SEQ ID NO: 11, CDR-H2 of an APOA-II antibody, Artificial sequence FINPSTGYTENNQRFN [0297] SEQ ID NO: 12, CDR-H3 of an APOA-II antibody, Artificial sequence RPYNPYAMDY [0298] SEQ ID NO: 13, CDR-L1 of an APOA-II antibody, Artificial sequence RASSSLSSSYLH [0299] SEQ ID NO: 14, CDR-L2 of an APOA-II antibody, Artificial sequence STSNLAS [0300] SEQ ID NO: 15, CDR-L3 of an APOA-II antibody, Artificial sequence QQFSVFPLT [0301] SEQ ID NO: 16, CDR-H1 of an APOA-II antibody, Artificial sequence NYGMN [0302] SEQ ID NO: 17, CDR-H2 of an APOA-II antibody, Artificial sequence WKNTYTGESTYADDFK [0303] SEQ ID NO: 18, CDR-H3 of an APOA-II antibody, Artificial sequence RDGSKYKIFDY [0304] SEQ ID NO: 19, CDR-L1 of an APOA-II antibody, Artificial sequence RASQDISNYLN [0305] SEQ ID NO: 20, CDR-L2 of an APOA-II antibody, Artificial sequence YTSRLQS [0306] SEQ ID NO: 21, CDR-L3 of an APOA-II antibody, Artificial sequence QQGNTLPYT [0307] SEQ ID NO: 22, CDR-H1 of an APOA-II antibody, Artificial sequence GYTFTSYWMH [0308] SEQ ID NO: 23, CDR-H2 of an APOA-II antibody, Artificial sequence FINPSTGYTENNQNFK [0309] SEQ ID NO: 24, CDR-H3 of an APOA-II antibody, Artificial sequence RTYNPYGMDY [0310] SEQ ID NO: 25, light chain variable region of an ApoE antibody, Artificial sequence DVLMTQTPLSLPVSLGDQASISCRSSQSIVHSNGNTYLEWYLQKPGQSPKLLIYKVSN RFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPYTFGGGTKLEIKR [0311] SEQ ID NO: 26, heavy chain variable region of an ApoE antibody, Artificial sequence 4906-4947-1849.2 67 Atty. Dkt. No.: 139886-2010 RVQLQQSGPGLVKPGASVKISCKASGYTFTDYYINWVRQRPGQGLEWIGWIFPGSGI TYYNEKFKGKATLTVDRSSSTAYMLLSSLTSEDSAVYFCARYAYGSPFAYWGQGTL VTVSA [0312] SEQ ID NO: 27, light chain variable region of an ApoE antibody, Artificial sequence DVLMTQTPLSLPVSLGDQASISCRSSQNIIHSNGNTYLEWFLQRPGQSPELLIYKVSNR FSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPYTFGGGTKLEIKR [0313] SEQ ID NO: 28, heavy chain variable region of an ApoE antibody, Artificial sequence QVQLQQSGPELVKPGASVKISCKASGYIFTDYYINWVKRRPGQGLEWIGWIFPGSGV SYYNEQFKGKATLTVDKPSNTAYIFLSRLTSEDSAVYFCARYYSSSPFAYWGQGTLV TVSA [0314] SEQ ID NO: 29, light chain variable region of an ApoE antibody, Artificial sequence DVLMTQTPLSLPVSLGDQASISCRSSQNIVYSNGNTYLEWYLQKPGQSPKLLIYKVSN RFSGVPDRFSGSGSGTYFTLKISRVEAEDLGIYYCFQGSHVPYTFGGGTKLEIKR [0315] SEQ ID NO: 30, heavy chain variable region of an ApoE antibody, Artificial sequence QVQLQQSGPDLVKPGASVKISCKASGYTFIDYYINWAKQRPGQGLEWIGWIFPGSGS TYYNEKFKGKATLTVDKSSSTAYMFLSSLTSEDSAVFFCARYYGSSPFAYWGQGTL VTVSA [0316] SEQ ID NO: 31, light chain variable region of an ApoE antibody, Artificial sequence DVLMTQTPLSLPVSLGDQASISCRSSQNIIHSNGNTYLEWFLQKPGQSPKLLIYKVSN RFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPYTFGGGTKLEIKR [0317] SEQ ID NO: 32, heavy chain variable region of an ApoE antibody, Artificial sequence QIQLQQSGPELVKPGASVKISCKASGYTFTDYYINWVRQRPGQGLEWIGWIYPESFN TYYNEKFKGKATLTVDTSSNTAYMQLSSLTSEDSAVYFCARYYVSSPFAYWGQGTL VTVSA [0318] SEQ ID NO: 33, light chain variable region of an ApoE antibody, Artificial sequence DVLMTQSPLSLPVSLGDQASISCRSSQSIVHRNGNTYLEWYLQKPGQSPKLLIYKVSN RFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPYTFGGGTKLEIRR [0319] SEQ ID NO: 34, heavy chain variable region of an ApoE antibody, Artificial sequence 4906-4947-1849.2 68 Atty. Dkt. No.: 139886-2010 QVQLQQSGPELVKPGASVKISCKASGYTFSDYYINWVKQRPGQGLEWIGWIFPGSGS SYYNEKFKGKATLTVDKSSRTAYMLLSSLTSEDSAVYFCARYYGSSPFAYWGQGTL VTVST [0320] SEQ ID NO: 35, CDR-L1 of the light chain variable region of SEQ ID NOS: 41, 43, 45 and 47 RSSQSIVHSNGNTYLE [0321] SEQ ID NO: 36, CDR-L2 of the light chain variable region of SEQ ID NOS: 41, 43, 45 and 47 KVSNRFS [0322] SEQ ID NO: 37, CDR-L3 of the light chain variable region of SEQ ID NOS: 41, 43, 45 and 47 FQGSHVPYT [0323] SEQ ID NO: 38, CDR-H1 of the heavy chain variable region of SEQ ID NOS: 42, 44, 46, 48 and 50 DYYIN [0324] SEQ ID NO: 39, CDR-H2 of the heavy chain variable region of SEQ ID NO: 26 WIFPGSGITYYNEKFKG [0325] SEQ ID NO: 40, CDR-H3 of the heavy chain variable region of SEQ ID NO: 26 YAYGSPFAY [0326] SEQ ID NO: 41, CDR-L1 of the light chain variable region of SEQ ID NOS: 43, 45, 47, and 49 RSSQNIIHSNGNTYLE [0327] SEQ ID NO: 42, CDR-H2 of the heavy chain variable region of SEQ ID NO: 28 WIFPGSGVSYYNEQFKG [0328] SEQ ID NO: 43, CDR-H3 of the heavy chain variable region of SEQ ID NO: 28 YYSSSPFAY [0329] SEQ ID NO: 44, CDR-L1 of the light chain variable region of SEQ ID NO: 29 RSSQNIVYSNGNTYLE [0330] SEQ ID NO: 45, CDR-H2 of the heavy chain variable region of SEQ ID NO: 30 WIFPGSGSTYYNEKFKG [0331] SEQ ID NO: 46, CDR-H3 of the heavy chain variable region of SEQ ID NOS: 46 and 50 YYGSSPFAY [0332] SEQ ID NO: 47, CDR-H2 of the heavy chain variable region of SEQ ID NO: 32 4906-4947-1849.2 69 Atty. Dkt. No.: 139886-2010 WIYPESFNTYYNEKFKG [0333] SEQ ID NO: 48, CDR-H3 of the heavy chain variable region of SEQ ID NO: 32 YYVSSPFAY [0334] SEQ ID NO: 49, CDR-L1 of the light chain variable region of SEQ ID NO: 33 RSSQSIVHRNGNTYLE [0335] SEQ ID NO: 50, CDR-H1 of the heavy chain variable region of SEQ ID NO: 34 WIFPGSGSSYYNEKFKG [0336] SEQ ID NO: 51, Homo Sapiens KRAS protein MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILD TAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVL VGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQRVEDAFYTLVREIRQYRLKKI SKEEKTPGCVKIKKCIIM [0337] SEQ ID NO: 52, Anti-APOA-I light chain IVMTQTPSSKSVPVGGTVTINCQASESVSSNNYLSWFQQKPGQPPKLLIYLASTLVSG VPSRFKGSGSGTQFTLTISDVVCDDAATYYCAGYKKRSTDVIAFGGGTEVVVKGDP VAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNS ADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC [0338] SEQ ID NO: 53, Anti-APOA-I heavy chain QEQLVESGGGLVQPEGSLALTCTASGFSFSTNYICWVRQAPGKGLEWVGCIDNGDA STYYASWAKGRFTISKTSSTTLTLQMTSLTAADTATYFCARYLAFDLWGPGTLVTVS SGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSV RQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPTCPPPELLGGP SVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQF NSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPP REELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPAVLDSDGSYFLYSKLSV PTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGK [0339] SEQ ID NO: 54, CDR-L1 Anti-APOA-I light chain QASESVSSNNYLS [0340] SEQ ID NO: 55, CDR-L2 Anti-APOA-I light chain LASTLVS [0341] SEQ ID NO: 56, CDR-L3 Anti-APOA-Ilight chain AGYKKRSTDVIA [0342] SEQ ID NO: 57, CDR-H1 Anti-APOA-I heavy chain GFSFSTN [0343] SEQ ID NO: 58, CDR-H2 Anti-APOA-I heavy chain DNGDAS [0344] SEQ ID NO: 59, CDR-H3 Anti-APOA-I heavy chain YLAFDL [0345] SEQ ID NO: 60, Anti- KRas-G12V light chain QVLTQTPSSVSAAVGGTVTINCQSSQSVYSTYCSWLQQKPGQPPKLLIYETSKLASGV PSRFRGSGSGTQFTLTISDLDCDDAATYYCLGGYDCSSGDCAAFGGGTEVVVKGDP 4906-4947-1849.2 70 Atty. Dkt. No.: 139886-2010 VAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNS ADCTYNLSSTLTLTSTQYNSHKEYTCKVTQGTTSVVQSFNRGDC [0346] SEQ ID NO: 61, Anti- KRas-G12V heavy chain QSVEESGGRLVTPGTPLTLTCTASGFDLSDYGMNWVRQAPGKGLEWIGFFASTSRSA YYASWAKGRFTISKTSTTVDLKITSPTTEDTATYFCARGGFLWGQGTLVTVSSGQPK APSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSVRQSSGL YSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPTCPPPELLGGPSVFIFPP KPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQFNSTIRV VSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPPREELSS RSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPAVLDSDGSYFLYSKLSVPTSEW QRGDVFTCSVMHEALHNHYTQKSISRSPGK [0347] SEQ ID NO: 62, CDR-L1 Anti- KRas-G12V light chain QSSQSVYSTYCS [0348] SEQ ID NO: 63, CDR-L2 Anti- KRas-G12V light chain ETSKLAS [0349] SEQ ID NO: 64, CDR-L3 Anti- KRas-G12V light chain LGGYDCSSGDCAA [0350] SEQ ID NO: 65, CDR-H1 Anti- KRas-G12V heavy chain GFDLSDY [0351] SEQ ID NO: 66, CDR-H2 Anti- KRas-G12V heavy chain ASTSRS [0352] SEQ ID NO: 67, CDR-H3 Anti- KRas-G12V heavy chain GGFL [0353] SEQ ID NO: 68, Tetravalent molecular hook construct heavy chain QEQLVESGGGLVQPEGSLALTCTASGFSFSTNYICWVRQAPGKGLEWVGCIDNGDA STYYASWAKGRFTISKTSSTTLTLQMTSLTAADTATYFCARYLAFDLWGPGTLVTVS SGQPKAPSVFPLAPCCGDTPSSTVTLGCLVKGYLPEPVTVTWNSGTLTNGVRTFPSV RQSSGLYSLSSVVSVTSSSQPVTCNVAHPATNTKVDKTVAPSTCSKPTCPPPELLGGP SVFIFPPKPKDTLMISRTPEVTCVVVDVSQDDPEVQFTWYINNEQVRTARPPLREQQF NSTIRVVSTLPIAHQDWLRGKEFKCKVHNKALPAPIEKTISKARGQPLEPKVYTMGPP REELSSRSVSLTCMINGFYPSDISVEWEKNGKAEDNYKTTPAVLDSDGSYFLYSKLSV PTSEWQRGDVFTCSVMHEALHNHYTQKSISRSPGKGGGGGSGGGGSGGGTGQSVEE SGGRLVTPGTPLTLTCTASGFDLSDYGMNWVRQAPGKGLEWIGFFASTSRSAYYAS WAKGRFTISKTSTTVDLKITSPTTEDTATYFCARGGFLWGQGTLVTVSSGGGGSGGG GSGGGGSQVLTQTPSSVSAAVGGTVTINCQSSQSVYSTYCSWLQQKPGQPPKLLIYE TSKLASGVPSRFRGSGSGTQFTLTISDLDSDDAATYYCLGGYDCSSGDCAAFGGGTE VVVK [0354] SEQ ID NO: 69, Tetravalent molecular hook construct heavy chain IVMTQTPSSKSVPVGGTVTINCQASESVSSNNYLSWFQQKPGQPPKLLIYLASTLVSG VPSRFKGSGSGTQFTLTISDVVCDDAATYYCAGYKKRSTDVIAFGGGTEVVVKGDP VAPTVLIFPPAADQVATGTVTIVCVANKYFPDVTVTWEVDGTTQTTGIENSKTPQNS ADCTYNLSSTLTLTSTQYNSHKEYTCK VTQGTTSVVQSFNRGDC [0355] SEQ ID NO: 70, Linker sequence 4906-4947-1849.2 71 Atty. Dkt. No.: 139886-2010 GGGGS [0356] SEQ ID NO: 71, Linker sequence GGGGSGGGGSGGGGS [0357] SEQ ID NO: 72, Linker sequence GGGGGSGGGGSGGG Equivalents [0358] 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 technology belongs. [0359] The present technology illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms “comprising,” “including,” “containing,” etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the present technology claimed. [0360] Thus, it should be understood that the materials, methods, and examples provided here are representative of preferred aspects, are exemplary, and are not intended as limitations on the scope of the present technology. [0361] It should be understood that although the present invention has been specifically disclosed by certain aspects, embodiments, and optional features, modification, improvement and variation of such aspects, embodiments, and optional features can be resorted to by those skilled in the art, and that such modifications, improvements and variations are considered to be within the scope of this disclosure. [0362] The present technology has been described broadly and generically herein. Each of the narrower species and sub-generic groupings falling within the generic disclosure also form part of the present technology. This includes the generic description of the present technology with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein. 4906-4947-1849.2 72 Atty. Dkt. No.: 139886-2010 [0363] In addition, where features or aspects of the present technology are described in terms of Markush groups, those skilled in the art will recognize that the present technology is also thereby described in terms of any individual member or subgroup of members of the Markush group. [0364] All publications, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entirety, to the same extent as if each were incorporated by reference individually. In case of conflict, the present specification, including definitions, will control. [0365] Other aspects are set forth within the following claims. 4906-4947-1849.2 73

Claims

Atty. Dkt. No.: 139886-2010 WHAT IS CLAIMED IS: 1. A method for intracellular delivery of a protein to a target cell in a subject in need thereof comprising administering to the subject (i) a protein-high-density lipoprotein (HDL) complex wherein the protein is tethered to the exterior of the high-density lipoprotein (HDL), or (ii) a protein-molecular hook complex, wherein the molecular hook is tethered to the exterior of the HDL molecule, wherein the protein is delivered intracellularly together with the HDL molecule, thereby delivering the protein to the target cell.

2. A method for delivering a protein into the interior of a target cell comprising contacting the cell with a protein-high-density lipoprotein (HDL) complex wherein the protein is tethered to the exterior of the HDL, optionally wherein the protein is tethered to the exterior of the HDL through a molecular hook, thereby delivering the protein to the interior of the target cell; optionally wherein the interior of the target cell comprises cytoplasm or nucleus.

3. The method of claim 2, wherein the contacting is performed in vitro or in vivo.

4. The method of claim 1, wherein the target cell of the subject is behind the blood brain barrier of the subject.

5. The method of claim 4, wherein the target cell of the subject is in the brain or the spine of the subject.

6. The method of any one of claims 1-5, wherein the molecular hook comprises a first antigen binding domain that specifically binds to an exterior facing protein of the HDL; and a second antigen binding domain that specifically binds to the protein.

7. The method of claim 6, wherein the exterior facing protein is selected from the group consisting of Apolipoprotein A-I (ApoA-I), Apolipoprotein A-II (ApoA-II), Apolipoprotein A-IV (ApoA-IV), Apolipoprotein B (ApoB), Apolipoprotein C-I (ApoC-I), Apolipoprotein C-II (Apo C-II), Apolipoprotein E (Apo E), Apolipoprotein L1 (ApoL-I), Apolipoprotein M (ApoM), Alpha-1-antitrypsin, Alpha-2-HS-glycoprotein, Complement C3, and Serum Amyloid A4.

8. The method of claim 6 or claim 7, wherein the first antigen binding domain comprises the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of a monoclonal antibody produced from a hybridoma of accession No. NITE BP-02442 or accession No. NITE BP-02443, 4906-4947-1849.2 74 Atty. Dkt. No.: 139886-2010 or wherein the first antigen binding domain comprises the amino acid sequences from a single line of the following table: wherein the first antigen binding domain comprises a light chain variable region as shown in SEQ ID NO: 52 and a heavy chain variable region as shown in SEQ ID NO: 53.

9. The method of claim 6 or claim 7, wherein the first antigen binding domain comprises the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the EPR2913 monoclonal antibody, or wherein the first antigen binding domain comprises amino acid sequences of a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15 SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 SEQ ID NO: 19 SEQ ID NO: 20 SEQ ID NO: 21 SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 .

10. The method of claim 6 or claim 7, wherein the first antigen binding domain comprises: (i) CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 sequences of the MAB41445 monoclonal antibody; (ii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 25 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 26; (iii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 27 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 28; (iv) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 29 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 30; (v) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 31 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 32; (vi) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 33 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 34; 4906-4947-1849.2 75 Atty. Dkt. No.: 139886-2010 (vii) a light chain variable region as shown in SEQ ID NO: 25 and a heavy chain variable region as shown in SEQ ID NO: 26; (vii) a light chain variable region as shown in SEQ ID NO: 27 and a heavy chain variable region as shown in SEQ ID NO: 28; (vii) a light chain variable region as shown in SEQ ID NO: 29 and a heavy chain variable region as shown in SEQ ID NO: 30; (vii) a light chain variable region as shown in SEQ ID NO: 31 and a heavy chain variable region as shown in SEQ ID NO: 32; or (vii) a light chain variable region as shown in SEQ ID NO: 33 and a heavy chain variable region as shown in SEQ ID NO: 34.

11. The method of claim 6 or claim 7, wherein the first antigen binding domain comprises the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the 3E4 monoclonal antibody.

12. The method of any one of claims 6-11, wherein the first antigen binding domain and/or the second antigen binding domain comprises an scFv, an (scFv)2, an scFvFc, a Fab, a Fab’, a F(ab’)₂, a bispecific antibody or a diabody.

13. The method of any one of claims 1-12, wherein the molecular hook further comprises a linker between the first antigen binding domain and the second antigen binding domain, optionally wherein the linker is an enzymatically cleavable linker, a hydrolysable linker, a pH sensitive linker, a photolabile linker, or a self immolative linker, or optionally wherein the linker is selected from any one of SEQ ID NOs: 70-72.

14. The method of any one of claims 1-13, wherein the protein is selected from the group consisting of an enzyme, a toxin, an interferon, a tumor suppressor, a protease, a recombinase, a hormone, and a stem cell transcription factor.

15. The method of any one of claims 1-13, wherein the protein is an antibody, an scFv, an (scFv)₂, an scFvFc, a Fab, a Fab’, a F(ab’)₂, a bispecific antibody or a diabody.

16. The method of claim 15, wherein the protein specifically binds a KRAS mutant selected from G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R, A146T, or K117N with respect to SEQ ID NO: 51.

17. The method of claim 16, wherein the protein comprises amino acid sequences from a single line of the following table: 4906-4947-1849.2 76 Atty. Dkt. No.: 139886-2010 CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 62 SEQ ID NO: 63 SEQ ID NO: 64 SEQ ID NO: 65 SEQ ID NO: 66 SEQ ID NO: 67 , or a light chain variable region as shown in SEQ ID NO: 60 and a heavy chain variable region as shown in SEQ ID NO: 61, or wherein the protein comprises a molecular hook that comprises a heavy chain comprising SEQ ID NO: 68 and a light chain that comprises SEQ ID NO: 69.

18. A method for delivering an antibody or an antigen binding fragment thereof to a target cell in a subject in need thereof comprising administering to the subject a molecular hook, wherein the molecular hook comprises the antigen binding domain of the antibody that specifically binds to an exterior facing protein of an HDL; and an antibody or an antigen binding fragment thereof, and wherein the molecular hook is tethered to the exterior of the HDL molecule, thereby delivering the antibody or an antigen binding fragment thereof antibody to the target cell in the subject.

19. The method of claim 18, wherein the exterior facing protein is selected from the group consisting of Apolipoprotein A-I (ApoA-I), Apolipoprotein A-II (ApoA-II), Apolipoprotein A-IV (ApoA-IV), Apolipoprotein B (ApoB), Apolipoprotein C-I (ApoC-I), Apolipoprotein C-II (Apo C-II), Apolipoprotein E (Apo E), Apolipoprotein L1 (ApoL-I), Apolipoprotein M (ApoM), Alpha-1-antitrypsin, Alpha-2-HS-glycoprotein, Complement C3, and Serum Amyloid A4.

20. The method of claim 18 or claim 19, wherein the antibody that specifically binds to an exterior facing protein of an HDL comprises the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of a monoclonal antibody produced from a hybridoma of accession No. NITE BP-02442 or accession No. NITE BP-02443, or wherein the antibody that specifically binds to an exterior facing protein of an HDL comprises amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 54 SEQ ID NO: 55 SEQ ID NO: 56 SEQ ID NO: 57 SEQ ID NO: 58 SEQ ID NO: 59 , or 4906-4947-1849.2 77 Atty. Dkt. No.: 139886-2010 a light chain variable region as shown in SEQ ID NO: 52 and a heavy chain variable region as shown in SEQ ID NO: 53.

21. The method of claim 18 or claim 19, wherein the antigen binding domain comprises the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the EPR2913 monoclonal antibody, or wherein the antigen binding domain comprises amino acid sequences of a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15 SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 SEQ ID NO: 19 SEQ ID NO: 20 SEQ ID NO: 21 SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 .

22. The method of claim 18 or claim 19, wherein the antigen binding domain of the antibody that specifically binds to an exterior facing protein of an HDL comprises: (i) CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 sequences of the MAB41445 monoclonal antibody; (ii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 25 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 26; (iii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 27 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 28; (iv) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 29 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 30; (v) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 31 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 32; (vi) CDR-L1, CDR-L2, and CDR-L3 sequences of CDR-L1, CDR-L2, and CDR-L3 of SEQ ID NO: 33 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 34; (vii) a light chain variable region as shown in SEQ ID NO: 25 and a heavy chain variable region as shown in SEQ ID NO: 26; (vii) a light chain variable region as shown in SEQ ID NO: 27 and a heavy chain variable region as shown in SEQ ID NO: 28; (vii) a light chain variable region as shown in SEQ ID NO: 29 and a heavy chain variable region as shown in SEQ ID NO: 30; 4906-4947-1849.2 78 Atty. Dkt. No.: 139886-2010 (vii) a light chain variable region as shown in SEQ ID NO: 31 and a heavy chain variable region as shown in SEQ ID NO: 32; or (vii) a light chain variable region as shown in SEQ ID NO: 33 and a heavy chain variable region as shown in SEQ ID NO: 34.

23. The method of claim 18 or claim 19, wherein the antigen binding domain of the antibody that specifically binds to an exterior facing protein of an HDL comprises the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the 3E4 monoclonal antibody.

24. The method of any one of claims 18-23, wherein the antigen binding domain of the antibody that specifically binds to an exterior facing protein of an HDL and/or the antibody or antigen binding fragment thereof comprises an scFv, an (scFv)2, an scFvFc, a Fab, a Fab’, a F(ab’)2, a bispecific antibody or a diabody.

25. The method of any one of claims 18-24, wherein the molecular hook further comprises a linker between the antigen binding domain of the antibody that specifically binds to an exterior facing protein of an HDL and the antibody or antigen binding fragment thereof, optionally wherein the linker is an enzymatically cleavable linker, a hydrolysable linker, a pH sensitive linker, a photolabile linker, or a self immolative linker, or optionally wherein the linker is selected from any one of SEQ ID NOs: 70-72.

26. A molecular hook comprising: (i) a first antigen binding domain that specifically binds to an exterior facing protein of a high density lipoprotein (HDL); and (ii) a second antigen binding domain that specifically binds to a protein, or a payload antibody or an antigen binding fragment thereof.

27. The molecular hook of claim 26, wherein the exterior facing protein is selected from the group consisting of Apolipoprotein A-I (ApoA-I), Apolipoprotein A-II (ApoA-II), Apolipoprotein A-IV (ApoA-IV), Apolipoprotein B (ApoB), Apolipoprotein C-I (ApoC-I), Apolipoprotein C-II (Apo C-II), Apolipoprotein E (Apo E), Apolipoprotein L1 (ApoL-I), Apolipoprotein M (ApoM), Alpha-1-antitrypsin, Alpha-2-HS-glycoprotein, Complement C3, and Serum Amyloid A4.

28. The molecular hook of claim 26 or claim 27, wherein the first antigen binding domain comprises the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of monoclonal antibody produced from a hybridoma of accession No. NITE BP- 02442 or accession No. NITE BP-02443, 4906-4947-1849.2 79 Atty. Dkt. No.: 139886-2010 or wherein the first antigen binding domain comprises amino acid sequences from a single line of the following table: wherein the first antigen binding domain comprises a light chain variable region as shown in SEQ ID NO: 52 and a heavy chain variable region as shown in SEQ ID NO: 53.

29. The molecular hook of claim 26 or claim 27, wherein the first antigen binding domain comprises the amino acid sequences of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the EPR2913 monoclonal antibody, or wherein the first antigen binding domain comprises amino acid sequences of a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 1 SEQ ID NO: 2 SEQ ID NO: 3 SEQ ID NO: 4 SEQ ID NO: 5 SEQ ID NO: 6 SEQ ID NO: 7 SEQ ID NO: 8 SEQ ID NO: 9 SEQ ID NO: 10 SEQ ID NO: 11 SEQ ID NO: 12 SEQ ID NO: 13 SEQ ID NO: 14 SEQ ID NO: 15 SEQ ID NO: 16 SEQ ID NO: 17 SEQ ID NO: 18 SEQ ID NO: 19 SEQ ID NO: 20 SEQ ID NO: 21 SEQ ID NO: 22 SEQ ID NO: 23 SEQ ID NO: 24 .

30. The molecular hook of claim 26 or claim 27, wherein the first antigen binding domain comprises: (i) CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the MAB41445 monoclonal antibody; (ii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 25 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 26; (iii) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 27 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 28; (iv) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 29 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 30; (v) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 31 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 32; (vi) CDR-L1, CDR-L2, and CDR-L3 sequences of SEQ ID NO: 33 and CDR-H1, CDR-H2 and CDR-H3 sequences of SEQ ID NO: 34; (vii) a light chain variable region as shown in SEQ ID NO: 25 and a heavy chain variable region as shown in SEQ ID NO: 26; 4906-4947-1849.2 80 Atty. Dkt. No.: 139886-2010 (vii) a light chain variable region as shown in SEQ ID NO: 27 and a heavy chain variable region as shown in SEQ ID NO: 28; (vii) a light chain variable region as shown in SEQ ID NO: 29 and a heavy chain variable region as shown in SEQ ID NO: 30; (vii) a light chain variable region as shown in SEQ ID NO: 31 and a heavy chain variable region as shown in SEQ ID NO: 32; or (vii) a light chain variable region as shown in SEQ ID NO: 33 and a heavy chain variable region as shown in SEQ ID NO: 34.

31. The molecular hook of claim 26 or claim 27, wherein the first antigen binding domain comprises CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDR-H3 of the 3E4 monoclonal antibody.

32. The molecular hook of any one of claims 26-31, wherein the protein is selected from the group consisting of an enzyme, a toxin, an interferon, a tumor suppressor, a protease, a recombinase, a hormone, and a stem cell transcription factor.

33. The molecular hook of any one of claims 26-32, wherein the protein is an antibody, an scFv, an (scFv)₂, an scFvFc, a Fab, a Fab’, a F(ab’)₂, a bispecific antibody or a diabody.

34. The molecular hook of claim 33, wherein the protein specifically binds a KRAS mutant selected from G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61H, Q61L, Q61R, A146T, or K117N with respect to SEQ ID NO: 51.

35. The molecular hook of claim 34, wherein the protein specifically binds a KRAS G12V mutant and comprises amino acid sequences from a single line of the following table: CDR-L1 CDR-L2 CDR-L3 CDR-H1 CDR-H2 CDR-H3 SEQ ID NO: 62 SEQ ID NO: 63 SEQ ID NO: 64 SEQ ID NO: 65 SEQ ID NO: 66 SEQ ID NO: 67 , or a light chain variable region as shown in SEQ ID NO: 60 and a heavy chain variable region as shown in SEQ ID NO: 61, or wherein the molecular hook comprises a heavy chain comprising SEQ ID NO: 68 and a light chain that comprises SEQ ID NO: 69.

36. The molecular hook of any one of claims 26-35, wherein the first antigen binding domain and or the second antigen binding domain or the payload antibody or antigen binding 4906-4947-1849.2 81 Atty. Dkt. No.: 139886-2010 fragment thereof comprises an scFv, an (scFv)2, an scFvFc, a Fab, a Fab’, a F(ab’)2, a bispecific antibody or a diabody.

37. The molecular hook of any one of claims 26-36, wherein the molecular hook comprises a linker between the first antigen binding domain and the second antigen binding domain or the payload antibody or antigen binding fragment thereof, optionally wherein the linker is an enzymatically cleavable linker, a hydrolysable linker, a pH sensitive linker, a photolabile linker, or a self immolative linker, or optionally wherein the linker is selected from any one of SEQ ID NOs: 70-72. 4906-4947-1849.2 82