Methods for using dual glycan binding AAV vectors
AssigneeThe University of North Carolina at Chapel Hill
InventorsAravind Asokan, Richard Samulski
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Abstract
Disclosed herein are methods for delivery of a nucleic acid to a subject for treatment of a disease, comprising administering a modified adeno-associated virus (AAV) vector that contains a therapeutic transgene comprising the nucleic acid in expressible form, further comprising a modified AAV2 capsid protein, comprising amino acid substitutions that introduce a galactose binding site from donor AAV9 capsid protein into the modified AAV2 capsid protein. Various diseases for treatment, such as kidney disease and liver disease, are disclosed. Various routes of administration are also disclosed.
Claims16
A method for delivery of a nucleic acid to a subject for treatment of a disease, comprising administering to the subject an adeno-associated virus (AAV) vector comprising:
- (a) a modified adeno-associated virus 2 (AAV2) capsid protein, comprising amino acid substitutions that result in the amino acid sequence:
- i) SVAGPSNMAVQGR at positions corresponding to amino acids 464-476 of AAV9 (SEQ ID NO:75);
- and
- ii) EFAW at positions corresponding to amino acids 500-503 of AAV9 (SEQ ID NO:75);
- wherein the amino acid substitutions introduce a galactose binding site from donor AAV9 capsid protein into the modified AAV2 capsid protein;
- and
- (b) a nucleic acid comprising at least one terminal repeat sequence and a nucleotide sequence encoding a therapeutic polypeptide or RNA operably associated with an expression control element, wherein the nucleic acid is encapsidated by the AAV capsid.
A method of introducing a nucleic acid into a subject having a kidney disease, comprising contacting a cell of the subject with an adeno-associated virus (AAV) vector comprising:
- (a) a modified adeno-associated virus 2 (AAV2) capsid protein, comprising amino acid substitutions that result in the amino acid sequence:
- i) SVAGPSNMAVQGR at positions corresponding to amino acids 464-476 of AAV9 (SEQ ID NO:75);
- and
- ii) EFAW at positions corresponding to amino acids 500-503 of AAV9 (SEQ ID NO:75);
- wherein the amino acid substitutions introduce a galactose binding site from donor AAV9 capsid protein into the modified AAV2 capsid protein;
- and
- (b) a nucleic acid comprising at least one terminal repeat sequence and a transgene selected to treat the kidney disease of the subject, wherein the nucleic acid is encapsidated by the AAV capsid.
Dependencies are inferred from the claim text.