# US 12,767,957 B2 · Engineered muscle targeting compositions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,767,957 B2 - Document ID: US12767957B2 - Status: Granted - Kind: B2 - Application number: 19/390,070 - Filed: 2025-11-14 - Published: 2026-03-12 - Granted: 2026-10-20 - Earliest claimed: 2019-10-16 - Assignees: The Broad Institute, Inc.; President and Fellows of Harvard College; Massachusetts Institute of Technology - Applicants: The Broad Institute, Inc.; President and Fellows of Harvard College; Massachusetts Institute of Technology - Inventors: Pardis Sabeti; Mohammadsharif Tabebordbar; Simon Ye - Web page: https://patentgrep.com/patent/US12767957B2 ## CPC - C12N 15/86: Viral vectors - A61K 31/7088: Compounds having three or more nucleosides or nucleotides - A61K 47/6435: {the peptide or protein in the drug conjugate being a connective tissue peptide, e.g. collagen, fibronectin or gelatin} - A61K 48/0066: {Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid} - C07K 7/06: having 5 to 11 amino acids - C07K 14/005: from viruses - C07K 14/47: from mammals - C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]} - C12N 15/11: DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity} - C07K 2319/01: containing a localisation/targetting motif - C12N 2310/20: involving clustered regularly interspaced short palindromic repeats [CRISPR] - C12N 2750/14122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2750/14123: Virus like particles [VLP] - C12N 2750/14143: viral genome or elements thereof as genetic vector - C12N 2750/14145: Special targeting system for viral vectors - C12N 2800/80: Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites - C12N 2810/405: Vectors comprising RGD peptide - C12N 2810/6027: ssDNA viruses - C12N 2830/008: cell type or tissue specific enhancer/promoter combination - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract Described herein are targeting moieties that can be capable of specifically targeting muscle cells and can include an n-mer motif. In some embodiments, the n-mer motif contains an RGD motif. Also described herein are vector systems, particles, polypeptides that can encode and/or contain one or more targeting moieties. Also described herein are methods of delivering a cargo to a cell, such as a muscle cell, using one or more of the targeting moieties described herein. ## Claims ### Claim 1 A composition comprising an adeno-associated virus (AAV) which comprises a targeting moiety effective to target a muscle cell and a polynucleotide encoding a cargo, wherein the targeting moiety comprises a viral capsid protein comprising a motif; which comprises XmRGDXn, wherein X is any amino acid, m is 1 or 2, and n is 4, and wherein the motif is (a) inserted between any two amino acids of the viral capsid protein, (b) replaces one or more native viral capsid protein amino acids, or both (a) and (b). ### Claim 2 (depends on 1) The composition of claim 1, wherein the motif is 8 amino acids in length. ### Claim 3 (depends on 1) The composition of claim 1, wherein the motif is 9 amino acids in length. ### Claim 4 (depends on 1) The composition of claim 1, wherein the motif is located at the N or C terminal of any amino acid in variable region VIII (VR-VIII). ### Claim 5 (depends on 1) The composition of claim 1, wherein the motif is located at the N or C terminal of any amino acid in amino acids 581 to 593 corresponding to the wild type AAV9 capsid protein. ### Claim 6 (depends on 1) The composition of claim 1, wherein the motif is located at the N or C terminal of any amino acid in variable region (VR-IV). ### Claim 7 (depends on 1) The composition of claim 1, wherein the motif is located at the N or C terminal of any amino acid in amino acids 452 and 460 corresponding to the wild type AAV9 capsid protein. ### Claim 8 (depends on 1) The composition of claim 1, wherein the viral capsid protein comprises an AAVRh74 capsid protein with one, two, or three amino acid substitution, insertion, or deletion. ### Claim 9 (depends on 4) The composition of claim 4, wherein the viral capsid protein comprises an AAVRh74 capsid protein with one, two, or three amino acid substitution, insertion, or deletion. ### Claim 10 (depends on 9) The composition of claim 9, wherein the amino acid sequence of the AAVRh74 capsid protein is different from the amino acid sequence of the wild type AAV9 capsid protein by 9 amino acids. ### Claim 11 (depends on 9) The composition of claim 9, wherein the amino acid sequence of the AAVRh74 capsid protein is different from the amino acid sequence of the wild type AAV9 capsid protein by 10 amino acids. ### Claim 12 (depends on 1) The composition of claim 1, wherein the viral capsid protein comprises an AAV9 capsid protein with one, two, or three amino acid substitution, insertion or deletion. ### Claim 13 (depends on 6) The composition of claim 6, wherein the viral capsid protein comprises an AAV9 capsid protein with one, two, or three additional amino acid substitution, insertion or deletion. ### Claim 14 (depends on 13) The composition of claim 13, wherein the amino acid sequence of the viral capsid protein is different from the amino acid sequence of the wild type AAV9 capsid protein by 9 amino acids. ### Claim 15 (depends on 13) The composition of claim 13, wherein the amino acid sequence of the viral capsid protein is different from the amino acid sequence of the wild type AAV9 capsid protein by 10 amino acids. ### Claim 16 (depends on 1) The composition of claim 1, wherein the cargo comprises a micro-dystrophin protein. ### Claim 17 (depends on 16) The composition of claim 16, wherein the cargo polynucleotide is operably linked to a promoter. ### Claim 18 (depends on 17) The composition of claim 17, wherein the promoter comprises a muscle-specific promoter. ### Claim 19 (depends on 18) The composition of claim 18, wherein the muscle-specific promoter comprises a MHCK7 promoter. ### Claim 20 (depends on 1) A method of targeting a muscle cell in a subject in need thereof having a muscular dystrophy comprising administering the composition of claim 1 to the subject, wherein the cargo is expressed in the muscle cell. ### Claim 21 (depends on 2) A method of targeting a muscle cell in a subject in need thereof having a muscular dystrophy comprising administering the composition of claim 2 to the subject, wherein the cargo is expressed in the muscle cell. ### Claim 22 (depends on 3) A method of targeting a muscle cell in a subject in need thereof having a muscular dystrophy comprising administering the composition of claim 3 to the subject, wherein the cargo is expressed in the muscle cell. ### Claim 23 (depends on 13) A method of targeting a muscle cell in a subject in need thereof having a muscular dystrophy comprising administering the composition of claim 13 to the subject, wherein the cargo is expressed in the muscle cell. ### Claim 24 (depends on 14) A method of targeting a muscle cell in a subject in need thereof having a muscular dystrophy comprising administering the composition of claim 14 to the subject, wherein the cargo is expressed in the muscle cell. ### Claim 25 (depends on 20) The method of claim 20, wherein the composition is capable of transducing the muscle cell more effectively than a composition comprising an AAV without the motif. ### Claim 26 (depends on 25) The method of claim 25, wherein the composition is capable of transducing the muscle cells by at least 50 times more effectively than the composition comprising an AAV without the motif. ### Claim 27 (depends on 25) The method of claim 25, wherein the composition is capable of transducing the muscle cells by about 50 to 100 times more effectively than the composition comprising an AAV without the motif. ### Claim 28 (depends on 20) The method of claim 20, wherein the composition is capable of inducing faster kinetics of in vivo gene expression in the muscle cell compared to a composition comprising an AAV without the motif. ### Claim 29 (depends on 20) The method of claim 20, wherein the composition is capable of expressing a micro-dystrophin protein in the muscle cell.