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

Patent metadata

Field	Value
Publication number	US-2016201088-A1
Application number	US-201615084615-A
Country	US
Kind code	A1
Filing date	Mar 30, 2016
Priority date	Dec 17, 2001
Publication date	Jul 14, 2016
Grant date	—

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

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 factor IX, 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 , further comprising one or more AAV inverted terminal repeat (ITR) sequence from an AAV heterologous to AAV8.

3 : The vector according to claim 2 , wherein the one or more AAV ITR is from AAV2.

4 : 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.

5 : The vector according to claim 4 , 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.

6 : The vector according to claim 5 , wherein said vp3 capsid protein has the sequence of aa 204 to 738 of SEQ ID NO: 2.

7 : 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.

8 : The vector according to claim 7 , 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.

9 : The vector according to claim 8 , wherein said vp1 capsid protein has the sequence of aa 1 to 738 of SEQ ID NO: 2.

10 : 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.

11 : The vector according to claim 10 , 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.

12 : The vector according to claim 11 , wherein said vp2 capsid protein has the sequence of aa 138 to 738 of SEQ ID NO: 2.

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

14 : A method of delivering a heterologous gene encoding factor IX to a cell, said method comprising contacting said cell with the vector according to claim 1 .

15 : The method according to claim 14 , comprising delivering said vector to a hepatocyte.

16 : A method for treating hemophilia B, said method comprising the step of contacting a cell with a vector according to claim 1 , wherein said vector directs expression of factor IX.

17 : A composition comprising at least the vector according to claim 1 and a pharmaceutically acceptable carrier.

18 : A composition comprising at least the vector according to claim 1 and a preservative or chemical stabilizer.

19 : 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 factor IX.

20 : 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 factor IX.

Assignees

• Univ Pennsylvania

Inventors

• Gao Guangping
• Wilsom 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