AAV4 vector and uses thereof
View Patent ↗The present invention provides an adeno-associated virus 4 (AAV4) virus and vectors and particles derived therefrom. In addition, the present invention provides methods of delivering a nucleic acid to a cell using the AAV4 vectors and particles.
1. A vector system for producing infectious virus particles having a characteristic of AAV4 comprising: at least one vector comprising an isolated nucleic acid sequence encoding an AAV4 capsid protein comprising an amino acid sequence at least 80% identical to SEQ ID NO:4, SEQ ID NO:16 or SEQ ID NO:18, wherein the AAV4 capsid protein is capable of forming a virus particle.
2. The vector system of claim 1 comprising a second vectors.
3. The vector system of claim 2 , wherein the first vector comprises a nucleic acid sequence encoding an AAV4 Rep protein comprising an amino acid sequence at least 80% identical to SEQ ID NO:2, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:11, wherein the AAV4 Rep protein has Rep protein activity, and the second vector comprises a pair of AAV inverted terminal repeats.
4. The vector system of claim 2 , wherein the first vector comprises a nucleic acid sequence encoding a second protein comprising an amino acid sequence at least 80% identical to SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:11, wherein the second protein has Rep protein activity, and the second vector comprises a pair of AAV inverted terminal repeats.
5. The vector system according to claim 3 , wherein the second vector comprises a pair of AAV2 inverted terminal repeats.
6. The vector system according to claim 3 , wherein the second vector comprises a pair of AAV3 inverted terminal repeats.
7. The vector system according to claim 3 , wherein the second vector comprises a pair of AAV4 inverted terminal repeats.
8. The vector system according to claim 7 , wherein the AAV4 inverted terminal repeats comprise a Rep protein binding site having four “GAGC” repeats, wherein in the fourth nucleotide in the first two “GAGC” repeats is a T rather than a C.
9. The vector system according to claim 8 , wherein the AAV4 inverted terminal repeats comprise the nucleotide sequence set forth in SEQ ID NO:6.
10. The vector system according to claim 8 , wherein the AAV4 inverted terminal repeats comprise the nucleotide sequence set forth in SEQ ID NO:20.
11. The vector system according to claim 3 , wherein the second vector comprises a pair of AAV5 inverted terminal repeats.
12. The vector system of claim 4 , wherein the adeno-associated virus 4 Rep protein has about 95% homology with the amino acid sequence set forth in SEQ ID NO:2.
13. The vector system of claim 4 , wherein the adeno-associated virus 4 Rep protein has the amino acid sequence set forth in SEQ ID NO:8.
14. The vector system of claim 4 , wherein the adeno-associated virus 4 Rep protein has about 95% homology with the amino acid sequence set forth in SEQ ID NO:8.
15. The vector system of claim 4 , wherein the adeno-associated virus 4 Rep protein has the amino acid sequence set forth in SEQ ID NO:9.
16. The vector system of claim 4 , wherein the adeno-associated virus 4 Rep protein has about 95% homology with the amino acid sequence set forth in SEQ ID NO:9
17. The vector system of claim 4 , wherein the adeno-associated virus 4 Rep protein has the amino acid sequence set forth in SEQ ID NO:10.
18. The vector system of claim 4 , wherein the adeno-associated virus 4 Rep protein has about 95% homology with the amino acid sequence set forth in SEQ ID NO:10.
19. The vector system of claim 4 , wherein the adeno-associated virus 4 Rep protein has the amino acid sequence set forth in SEQ ID NO:11.
20. The vector system of claim 4 , wherein the adeno-associated virus 4 Rep protein has about 95% homology with the amino acid sequence set forth in SEQ ID NO:11.
21. The vector system of claim 3 , wherein the first vector further comprises a nucleic acid encoding an AAV5 Rep protein.
22. The vector system according to claim 4 , wherein the first vector further comprises a nucleic acid encoding an AAV2 capsid protein.
23. The vector system according to claim 4 , wherein the first vector further comprises a nucleic acid encoding an AAV3 capsid protein.
24. The vector system of claim 4 , wherein the adeno-associated virus 4 capsid protein has the amino acid sequence set forth in SEQ ID NO:4.
25. The vector system of claim 4 , wherein the adeno-associated virus 4 capsid protein has the amino acid sequence defined by amino acids 438-601 set forth in SEQ ID NO:4.
26. The vector system of claim 4 , wherein the adeno-associated virus 4 capsid protein has about 98% homology to the amino acid sequence set forth in SEQ ID NO:4.
27. The vector system of claim 4 , wherein the adeno-associated virus 4 capsid protein has the amino acid sequence set forth in SEQ ID NO:16.
28. The vector system of claim 4 , wherein the adeno-associated virus 4 capsid protein has about 98% homology to the amino acid sequence set forth in SEQ ID NO:16.
29. The vector system of claim 4 , wherein the adeno-associated virus 4 capsid protein has the amino acid sequence set forth in SEQ ID NO:18.
30. The vector system of claim 4 , wherein the adeno-associated virus 4 capsid protein has about 98% homology to the amino acid sequence set forth in SEQ ID NO:18.
31. The vector system according to claim 4 , wherein the first vector further comprises a nucleic acid encoding an AAV5 capsid protein.
32. A vector system according to claim 3 , wherein the second vector further comprises a promoter between the inverted terminal repeats.
33. A vector system according to claim 32 , wherein the promoter is functionally linked to an exogenous nucleic acid.
34. A method of making a recombinant particle for delivering an exogenous nucleic acid to a cell, comprising delivering to a cell having helper function the vectors of the vector system of claim 33 .
35. The method of claim 34 , wherein the helper function is provided by a helper virus.