Adeno-associated virus compositions for targeted gene therapy

A recombinant AAV (rAAV), the rAAV comprising:

• a) a variant AAV capsid comprising a variant AAV capsid protein comprising an amino acid substitution of three or more amino acids within a 7-mer peptide sequence of a parental AAV capsid protein, wherein the 7-mer peptide sequence is from amino acid positions that correspond to amino acid residues 452-458 of AAV9 VP1 (SEQ ID NO:1), and wherein the amino acid substitution is not ILGTGTS (SEQ ID NO:
• 45479), not QSSQTPR (SEQ ID NO:
• 45480), and not TLAVPFK (SEQ ID NO:
• 45477);
• and
• b) a heterologous polynucleotide comprising a nucleotide sequence encoding a gene product,
• wherein the variant AAV capsid has an increased tropism for a target cell or tissue, when measured in a subject, relative to a tropism of the parental AAV capsid,
• wherein the target cell or tissue is selected from the group consisting of a central nervous system (CNS) cell, a peripheral nervous system (PNS) cell, lung tissue, intestinal tissue, heart tissue, stomach tissue, and a combination thereof.