Methods and compositions for dual glycan binding AAV vectors
View Patent ↗The present invention provides methods and compositions comprising an adeno-associated virus (AAV) capsid protein, comprising one or more amino acids substitutions, wherein the substitutions introduce a new glycan binding site into the AAV capsid protein.
1. An adeno-associated virus 2 (AAV2) capsid protein comprising an AAV2 capsid amino acid sequence into which the following substitutions have been introduced, based on the amino acid sequence of SEQ ID NO:65: A266S, Q464V, A467P, D469N, I470M, R471A, D472V, S474G, Y500F and S501A (AAV2 VP1 numbering).
2. An adeno-associated virus 2 (AAV2) capsid protein comprising an AAV2 capsid amino acid sequence into which the following substitutions have been introduced, based on the amino acid sequence of SEQ ID NO:65: A266S, Q464V, A467P, D469N, I470M, R471A, D472V, S474G, Y500F and S501A, and wherein amino acids 585-590 are substituted with QQNTAP (AAV2 VP1 numbering).
3. An adeno-associated virus 8 (AAV8) capsid protein comprising an AAV8 capsid amino acid sequence into which the following substitutions have been introduced, based on the amino acid sequence of SEQ ID NO:66: A269S, Q467V, N471S, N475V, A477G, K478R, N502E (AAV8 VP1 numbering).
4. An AAV capsid comprising the AAV capsid protein of claim 1 .
5. A virus vector comprising:
(a) the AAV capsid of claim 4 ; and
(b) a nucleic acid comprising at least one terminal repeat sequence, wherein the nucleic acid is encapsidated by the AAV capsid.
6. A composition comprising the virus vector of claim 5 in a pharmaceutically acceptable carrier.
7. A method of introducing a nucleic acid into a cell, comprising contacting the cell with the virus vector of claim 5 .
8. The method of claim 7 , wherein the cell is in a subject.
9. The method of claim 8 , wherein the subject is a human subject.
10. An AAV capsid comprising the AAV capsid protein of claim 2 .
11. A virus vector comprising:
(a) the AAV capsid of claim 10 ; and
(b) a nucleic acid comprising at least one terminal repeat sequence, wherein the nucleic acid is encapsidated by the AAV capsid.
12. A composition comprising the virus vector of claim 11 in a pharmaceutically acceptable carrier.
13. A method of introducing a nucleic acid into a cell, comprising contacting the cell with the virus vector of claim 11 .
14. The method of claim 13 , wherein the cell is in a subject.
15. The method of claim 14 , wherein the subject is a human subject.
16. An AAV capsid comprising the AAV capsid protein of claim 3 .
17. A virus vector comprising:
(a) the AAV capsid of claim 16 ; and
(b) a nucleic acid comprising at least one terminal repeat sequence, wherein the nucleic acid is encapsidated by the AAV capsid.
18. A composition comprising the virus vector of claim 17 in a pharmaceutically acceptable carrier.
19. A method of introducing a nucleic acid into a cell, comprising contacting the cell with the virus vector of claim 17 .
20. The method of claim 19 , wherein the cell is in a subject.
21. The method of claim 20 , wherein the subject is a human subject.