AAV chimeras
Provided herein are compositions and methods for packaging a recombinant adeno-associated vims (rAAV) particle comprising using inverted terminal repeats (ITRs) and rep genes of different serotypes and/or using chimeric rep genes.
1. A composition comprising: a nucleic acid sequence comprising a rep gene that encodes a chimeric rep protein, wherein the rep gene comprises at least one nucleic acid sequence from a rep gene of a first AAV serotype and at least one nucleic acid sequence from a rep gene of a second AAV serotype, wherein the first AAV serotype is AAV1 or AAV8, wherein the second AAV serotype is AAV2, and wherein the chimeric rep protein exhibits a higher rAAV nucleic acid packaging efficiency when introduced into a cell as compared to a nonchimeric rep protein of said first or second AAV serotype.
2. The composition of claim 1 , wherein the at least one nucleic acid sequence from the rep gene of the first AAV serotype or the at least one nucleic acid sequence from the rep gene of the second AAV serotype encodes at least a portion of a domain selected from the group consisting of: a DNA binding domain, a helicase domain, a Nuclear Localization Signal/p40 promoter domain, and a zinc finger domain.
3. The composition of claim 1 , wherein the at least one nucleic acid sequence from the rep gene of the first AAV serotype or the at least one nucleic acid sequence from the rep gene of the second AAV serotype encodes at least a portion of a DNA binding domain or a zinc finger domain.
4. The composition of claim 1 , wherein the rep gene further comprises at least one nucleic acid sequence from a rep gene of a third AAV serotype, wherein the third AAV serotype is different from the first and the second AAV serotypes.
5. The composition of claim 1 , wherein the nucleic acid sequence further comprises a cap gene from the first AAV serotype or the second AAV serotype.