Antibody-evading virus vectors
The present disclosure provides recombinant AAV capsid proteins comprising a modification in the amino acid sequence and virus vectors comprising the recombinant AAV capsid proteins. The disclosure also provides methods of administering the virus vectors and vims capsids of the disclosure to a cell or to a subject in vivo.
1. An adeno-associated virus (AAV) vector comprising an AAV capsid protein, wherein the AAV capsid protein comprises the amino acid sequence of SEQ ID NO: 380.
2. The AAV vector of claim 1 , wherein the AAV vector comprises an encapsidated nucleic acid, wherein the encapsidated nucleic acid is encapsidated by the AAV capsid protein.
3. The AAV vector of claim 2 , wherein the encapsidated nucleic acid comprises at least one terminal repeat sequence.
4. The AAV vector of claim 3 , wherein the encapsidated nucleic acid further comprises a heterologous nucleic acid sequence.
5. The AAV vector of claim 4 , wherein the encapsidated nucleic acid comprises a first inverted terminal repeat (ITR) sequence located 3′ of the heterologous nucleic acid sequence and a second inverted terminal repeat (ITR) sequence located 5′ of the heterologous nucleic acid sequence.
6. The AAV vector of claim 4 , wherein the heterologous nucleic acid sequence encodes a polypeptide.
7. The AAV vector of claim 6 , wherein the polypeptide is a therapeutic polypeptide.
8. The AAV vector of claim 6 , wherein the polypeptide is an immunogenic polypeptide.
9. The AAV vector of claim 6 , wherein the polypeptide is nuclease.
10. The AAV vector of claim 9 , wherein the nuclease is a Cas9 nuclease or a Cpf1 nuclease.
11. The AAV vector of claim 4 , wherein the heterologous nucleic acid sequence encodes an untranslated RNA.
12. The AAV vector of claim 11 , wherein the untranslated RNA is a guide RNA.
13. The AAV vector of claim 11 , wherein the untranslated RNA is an antisense RNA, a ribozyme, or an interfering RNA.
14. A pharmaceutical composition comprising the AAV vector of claim 2 and a pharmaceutically acceptable carrier.
15. A method of introducing a nucleic acid into a cell, comprising contacting the cell with the AAV vector of claim 2 .
16. An adeno-associated virus (AAV) capsid protein comprising the amino acid sequence of SEQ ID NO: 380.
17. A nucleic acid comprising a nucleic acid sequence encoding the AAV capsid protein of claim 16 .
18. An expression vector comprising a nucleic acid sequence encoding the AAV capsid protein of claim 17 .
19. A cell comprising the nucleic acid of claim 17 .
20. A method of producing an adeno-associated virus (AAV) vector, the method comprising:
a. culturing a cell that comprises (i) the nucleic acid of claim 17 , (ii) a nucleic acid comprising 5′ inverted terminal repeat (ITR), a heterologous nucleic acid sequence, and a 3′ ITR, and (iii) AAV sequences sufficient for replication and encapsidation of nucleic acid, wherein the cell is cultured under conditions such that it produces the AAV vector; and
b. collecting the AAV vector from the cell.