Recombinant AAVS having useful transcytosis properties
The disclosure in some aspects relates to recombinant adeno-associated viruses having distinct tissue targeting capabilities. In some aspects, the disclosure relates to gene transfer methods using the recombinant adeno-associate viruses. In some aspects, the disclosure relates to isolated AAV capsid proteins and isolated nucleic acids encoding the same.
1. A recombinant AAV (rAAV) comprising an AAV capsid protein having an amino acid sequence selected from the group consisting of: SEQ ID NOs: 3-7.
2. A composition comprising the recombinant rAAV of claim 1 .
3. The composition of claim 2 further comprising a pharmaceutically acceptable carrier.
4. A method for delivering a transgene to a subject comprising administering the rAAV of claim 1 to a subject, wherein the rAAV comprises
at least one transgene, and wherein the rAAV infects cells of a target tissue of the subject.
5. The method of claim 4 , wherein the at least one transgene encodes a CNS-protein or a secreted tumor suppressor protein.
6. The method of claim 5 , wherein the CNS-protein is aspartoacylase (ASPA), or wherein the secreted tumor suppressor protein is IGFBP7 or SRPX.
7. The method of claim 6 , wherein the ASPA is human ASPA.
8. The method of claim 4 , wherein the at least one transgene encodes an immunoglobulin heavy chain or light chain or fragment thereof.
9. The method of claim 4 , wherein the at least one transgene encodes a miRNA, miRNA sponge, or TuD RNA.
10. The method of claim 9 , wherein the miRNA is expressed in a cell of the target tissue.
11. The method of claim 4 , wherein the rAAV is administered to the subject intravenously, transdermally, intraocularly, intrathecally, orally, intramuscularly, subcutaneously, intranasally, or by inhalation.
12. An isolated nucleic acid comprising a sequence selected from the group consisting of: SEQ ID NOs: 10-14, or encoding an AAV capsid protein having an amino acid sequence selected from the group consisting of SEQ ID NOs: 3-7.
13. An isolated AAV capsid protein comprising an amino acid sequence selected from the group consisting of: SEQ ID NOs: 3-7.
14. A composition comprising the isolated AAV capsid protein of claim 13 .
15. The composition of claim 14 further comprising a pharmaceutically acceptable carrier.
16. A method for treating Canavan disease, the method comprising administering to a subject a therapeutically effective amount of a rAAV to a subject, wherein the rAAV comprises:
(i) the isolated capsid protein of claim 13 , and
(ii) at least one transgene, wherein the at least one transgene encodes ASPA;
and wherein the rAAV infects cells of a target tissue of the subject.
17. The method of claim 16 , wherein the target tissue is CNS tissue.
18. A method for treating cancer, the method comprising administering to a subject a therapeutically effective amount of a rAAV to a subject, wherein the rAAV comprises:
(i) the isolated capsid protein of claim 13 , and
(ii) at least one transgene, wherein the at least one transgene encodes a tumor suppressor protein;
and wherein the rAAV infects cells of a target tissue of the subject.
19. The method of claim 18 , wherein the tumor suppressor protein is selected from the group consisting of IGFBP7 and SRPX.