Chimeric capsids
The present invention relates to viral vectors and methods of their production and use.
1. An adeno-associated virus (AAV) capsid protein, said AAV capsid protein comprising a chimeric polypeptide which has at least 95% identity with a reference sequence comprising SEQ ID NO: 436; wherein the chimeric polypeptide is a substitutional variant of SEQ ID NO: 436; and
wherein the VRVIII-CNS domain of SEQ ID NO: 436 is replaced with a donor sequence selected from any one of SEQ ID NOs: 547 or 549-553.
2. The AAV capsid protein of claim 1 , wherein the donor sequence is SEQ ID NO: 547.
3. The AAV capsid protein of claim 1 , wherein the donor sequence is SEQ ID NO: 549.
4. The AAV capsid protein of claim 1 , wherein the donor sequence is SEQ ID NO: 550.
5. The AAV capsid protein of claim 1 , wherein the donor sequence is SEQ ID NO: 551.
6. The AAV capsid protein of claim 1 , wherein the donor sequence is SEQ ID NO: 552.
7. The AAV capsid protein of claim 1 , wherein the donor sequence is SEQ ID NO: 553.
8. An adeno-associated virus (AAV) particle comprising the AAV capsid protein of claim 1 and a vector genome which comprises a payload construct.
9. The AAV particle of claim 8 , wherein the payload construct comprises a polynucleotide sequence encoding a therapeutic protein.
10. The AAV particle of claim 8 , wherein the payload construct comprises a polynucleotide sequence encoding an siRNA, an shRNA, an miRNA, or a precursor thereof.