Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor

Patent metadata

Field	Value
Publication number	US-9493788-B2
Application number	US-201514598462-A
Country	US
Kind code	B2
Filing date	Jan 16, 2015
Priority date	Dec 17, 2001
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

Sequences of a serotype 8 adeno-associated virus and vectors and host cells containing these sequences are provided. Also described are methods of using such host cells and vectors in production of rAAV particles.

First claim

The invention claimed is:

1. An adeno-associated virus (AAV)8 viral vector comprising an AAV8 capsid having packaged therein a heterologous gene operably linked to regulatory sequences which direct its expression, wherein the heterologous gene encodes ornithine transcarbamylase (OTC), wherein the AAV8 capsid comprises a vp3 capsid protein having the sequence of aa 204 to 738 of SEQ ID NO: 2, or a sequence which is at least 95% identical to said sequence of aa 204 to 738 of SEQ ID NO: 2.

2. The vector according to claim 1 , wherein said OTC is human OTC.

3. The vector according to claim 1 , further comprising one or more AAV inverted terminal repeat (ITR) sequence from an AAV heterologous to AAV8.

4. The vector according to claim 3 , wherein the one or more AAV ITR is from AAV2.

5. A composition comprising the vector according to claim 1 and a pharmaceutically acceptable carrier.

6. A host cell containing the vector according to claim 1 in culture.

7. A method for treating OTC deficiency, said method comprising the step of contacting a cell with a vector according to claim 1 , wherein said vector directs expression of OTC.

8. The method according to claim 7 , wherein said vector is delivered via intravenous administration.

9. A composition comprising the vector according to claim 1 and a preservative or chemical stabilizer.

10. The vector according to claim 1 , wherein said vp3 capsid protein has a sequence which is at least 95% identical to the sequence of aa 204 to 738 of SEQ ID NO: 2.

11. The vector according to claim 10 , wherein said vp3 capsid protein has a sequence at least 99% identical to the sequence of aa 204 to 738 of SEQ ID NO: 2.

12. The vector according to claim 10 , wherein said vp3 capsid protein has the sequence of aa 204 to 738 of SEQ ID NO: 2.

13. The vector according to claim 1 , wherein said AAV8 capsid further comprises a vp1 capsid protein having a sequence which is at least 95% identical to the sequence of aa 1 to 738 of SEQ ID NO: 2.

14. The vector according to claim 13 , wherein said vp1 capsid protein has an amino acid sequence at least 99% identical to the sequence of aa 1 to 738 of SEQ ID NO: 2.

15. The vector according to claim 13 , wherein said vp1 capsid protein has the sequence of aa 1 to 738 of SEQ ID NO: 2.

16. The vector according to claim 1 , wherein said AAV8 capsid further comprises a vp2 capsid protein having a sequence which is at least 95% identical to the sequence of aa 138 to 738 of SEQ ID NO: 2.

17. The vector according to claim 16 , wherein said vp2 capsid protein has an amino acid sequence at least 99% identical to the sequence of aa 138 to 738 of SEQ ID NO: 2.

18. The vector according to claim 16 , wherein said vp2 capsid protein has the sequence of aa 138 to 738 of SEQ ID NO: 2.

19. A method of delivering a heterologous gene encoding ornithine transcarbamylase (OTC) to a cell, said method comprising contacting said cell with the vector according to claim 1 .

20. The method according to claim 19 , comprising delivering said vector to a hepatocyte.

21. A composition comprising at least an adeno-associated virus (AAV) vector and a physiologically compatible carrier, the AAV vector comprising an AAV capsid comprising at least an AAV8 vp3 capsid protein having a sequence comprising amino acids 204 to 738 of SEQ ID NO: 2 or an amino acid sequence at least 95% identical thereto, said capsid having packaged therein a heterologous gene operably linked to regulatory sequences which direct its expression, wherein the heterologous gene encodes ornithine transcarbamylase (OTC).

22. A composition comprising at least an adeno-associated virus (AAV) vector and a physiologically compatible carrier, the AAV vector comprising an AAV capsid comprising at least an AAV8 vp1 capsid protein having a sequence comprising amino acids 1 to 738 of SEQ ID NO: 2 or an amino acid sequence at least 95% identical thereto, said capsid having packaged therein a heterologous gene operably linked to regulatory sequences which direct its expression, wherein the heterologous gene encodes ornithine transcarbamylase (OTC).

Assignees

• Univ Pennsylvania

Inventors

• Gao Guangping
• Wilson James M
• Alvira Mauricio R

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P1/18

  for pancreatic disorders, e.g. pancreatic enzymes · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title