Adeno-associated virus compositions for targeted gene therapy

The rAAV of claim 4, wherein the three or more amino acids comprises three or more of:

• a) A, D, G, L, N, Q, S, or T substituted at an amino acid at a position corresponding to amino acid residue 452 of AAV9 VP1 (SEQ ID NO:
• 1);
• b) A, G, N, P, Q, R, S, or substituted at an amino acid at a position corresponding to amino acid residue 453 of AAV9 VP1 (SEQ ID NO:
• 1);
• c) A, D, G, N, S, or T substituted at an amino acid at a position corresponding to amino acid residue 454 of AAV9 VP1 (SEQ ID NO:
• 1);
• d) A, D, G, K, N, P, Q, S, or T substituted at an amino acid at a position corresponding to amino acid residue 455 of AAV9 VP1 (SEQ ID NO:
• 1);
• e) A, G, K, N, P, R, S, or T substituted at an amino acid at a position corresponding to amino acid residue 456 of AAV9 VP (SEQ ID NO:
• 1);
• f) A, G, K, N, P, R, S, T, or V substituted at an amino acid at a position corresponding to amino acid residue 457 of AAV9 VP1 (SEQ ID NO:
• 1);
• and
• g) A, G, K, L, R, S, T, or V substituted at an amino acid at a position corresponding to amino acid residue 458 of AAV9 VP1 (SEQ ID NO:
• 1).

A recombinant AAV (rAAV), the rAAV comprising:

• a) a variant AAV5 of AAV9 capsid comprising a variant AAV capsid protein comprising a substitution of three or more amino acids relative to the corresponding parental AAV capsid protein, that insertion or substitution residing in the loop corresponding to the amino acid 455 loop (AA455 loop), and wherein the amino acid substitution does not result in the consecutive peptide sequences ILGTGTS (SEQ ID NO:
• 45479), QSSQTPR (SEQ ID NO:
• 45480), or TLAVPFK (SEQ ID NO:
• 45477) in the AA455 loop;
• and
• b) a heterologous polynucleotide comprising a nucleotide sequence encoding a gene product.