Methods and compositions for dual glycan binding AAV vectors

Patent metadata

Field	Value
Publication number	US-10077291-B2
Application number	US-201414777070-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Sep 18, 2018
Grant date	Sep 18, 2018

Abstract

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.

First claim

That which is claimed is:

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.

Assignees

• Univ North Carolina Chapel Hill

Inventors

• Asokan Aravind
• Samulski Richard

Classifications

• A61P31/18

  for HIV · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P31/22

  for herpes viruses · CPC title