Capsid-modified, rAAV3 vector compositions and methods of use in gene therapy of human liver cancer

A modified AAV capsid protein comprising any one of the following combinations of non-native amino acid substitutions:

• (a) Y705F, Y731F, and any one of the following:
• (i) T492V;
• (ii) K533R;
• (iii) S663V;
• (iv) S663V, and T492V;
• or
• (v) S663V, T492V, and K533R;
• or
• (b) S663V, T492V and K533R;
• of the wild-type AAV3 capsid protein as set forth in SEQ ID NO:3, or at the equivalent surface-exposed amino acid residues in any one of the corresponding wild-type AAV1, AAV2, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAV10 capsid proteins, as set forth in SEQ ID NO:
• 1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, respectively, or in any combination thereof, or
• (c) Y444F and T550V;
• (d) S458V and S492V, but not S662V;
• or
• (e) Y444F, Y500F, Y730F and S458V;
• of the wild-type AAV2 capsid protein as set forth in SEQ ID NO:2, or at the equivalent surface-exposed amino acid residues in any one of the corresponding wild-type AAV1, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, or AAV10 capsid proteins, as set forth in SEQ ID NO:
• 1, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:10, respectively, or in any combination thereof.