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AssigneeAD Molecular Therapeutics Inc.
InventorsDavid H. Kirn, Melissa Kotterman, David Schaffer
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Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of muscle cells as compared to the infectivity of the muscle cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more muscle cells for the treatment of muscle disorders and diseases.
A method for delivering a heterologous nucleic acid encoding a gene product to a muscle cell, the method comprising contacting the muscle cell with a recombinant adeno-associated virus (rAAV), the rAAV comprising (i) the heterologous nucleic acid and (ii) a variant AAV capsid protein comprising a peptide insertion with a length of 7 to 13 amino acids covalently inserted in the GH-loop of the capsid protein relative to a corresponding parental AAV capsid protein, wherein the peptide insertion comprises the amino acid sequence NKTTNKD (SEQ ID NO:
A method for treating a disease selected from Fabry disease, Friedreich's ataxia, Duchenne's muscular dystrophy, Pompe disease, and myophosphorylase deficiency, the method comprising administering to a subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a recombinant adeno-associated virus (rAAV), the rAAV comprising (i) a heterologous nucleic acid comprising a nucleotide sequence encoding a protein selected from alpha galactosidase A (GLA), frataxin (FXN), dystrophin (DMD)), acid alpha glucosidase (GAA), and muscle glycogen phosphorylase (PYGM) and (ii) a variant AAV capsid protein comprising a peptide insertion with a length of 7 to 13 amino acids covalently inserted in the GH-loop of the capsid protein relative to a corresponding parental AAV capsid protein, wherein the peptide insertion comprises the amino acid sequence NKTTNKD (SEQ ID NO:
Dependencies are inferred from the claim text.