High efficiency library-identified AAV vectors
Aspects of the disclosure relate to barcoded chimeric adeno-associated virus (AAV) capsid libraries, chimeric capsids and related recombinant AAVs (rAAVs) identified using the libraries. Specifically, the chimeric AAV capsid libraries comprise a plurality of nucleic adds encoding AAV capsid proteins, wherein each nucleic acid (i) encodes a unique AAV capsid protein having distinct polypeptide regions of greater than six amino acids in length that are derived from at least two different AAV serotypes, and (ii) comprises a unique barcode sequence. Further disclosed are methods of preparing an AAV library and identifying AAV capsids tropic for a target tissue.
1. A chimeric AAV capsid protein comprising distinct polypeptide regions derived from at least three different AAV serotypes selected from the group consisting of: AAV1, AAV2, AAV4, AAV5, AAV6, AAV8, AAV9, AAVrh8, AAVrh10, AAVrh39, and AAVrh43, wherein the chimeric AAV capsid protein comprises the sequence as set forth in any one of SEQ ID NOs: 5-8.
2. A rAAV comprising the chimeric AAV capsid protein of claim 1 .
3. The rAAV of claim 2 , wherein the rAAV targets the CNS tissue of a subject.
4. The rAAV of claim 3 , further comprising a transgene, wherein the transgene comprises a CNS-associated gene.