Adeno associated virus plasmids and vectors

Patent metadata

Field	Value
Publication number	US-9677088-B2
Application number	US-201314399428-A
Country	US
Kind code	B2
Filing date	May 9, 2013
Priority date	May 9, 2012
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

Disclosed herein are adeno associated viral plasmids and viral vectors. Also disclosed are methods of using adeno associated viral vectors.

First claim

The invention claimed is:

1. An adeno associated virus plasmid comprising:
a polynucleotide that encodes a protein with the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least about 60%, at least about 75%, at least about 80%, at least about 90%, or at least about 95% sequence identity to SEQ ID NO: 1, wherein the protein further comprises a mutation at at least one of L380, T381, L382, N383, I440, D441, Y446, L447, I450, T451, V465, S469, N470, M471, Q474, G475, Y484, R485, E500, W503, P504, R514, N515, S516, and L517.

2. The adeno associated virus plasmid of claim 1 , wherein the mutation is at at least one of I451, V465, S469, N470, M471, G475, Y484, E500, N515, and L517.

3. The adeno associated virus plasmid of claim 1 , wherein the mutation is at least one of Y484A and R485A.

4. The adeno associated virus plasmid of claim 1 , wherein the mutation is in a viral capsid protein.

5. An adeno associated virus plasmid comprising:
a polynucleotide that encodes a protein with the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence having at least about 60%, at least about 75%, at least about 80%, at least about 90%, or at least about 95% sequence identity to SEQ ID NO: 4, the protein further comprises a mutation at at least one of Q464, A467, D469, I470, R471, D472, S474, S501, and D514.

6. The adeno associated virus plasmid of claim 5 , wherein the mutation is at least one of Q464R, Q464V, A467P, D469G, D469T, I470M, R471A, R471S, D472V, D472E, D472N, S474P, S474A, S474G, S501F, and D514R.

7. An adeno associated virus plasmid comprising:
a polynucleotide that encodes a protein with an amino acid sequence selected from at least one of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 24, and SEQ ID NO: 25.

8. The adeno associated virus plasmid of claim 5 , wherein the mutation is in a viral capsid protein.

9. The plasmid of claim 1 , wherein the polynucleotide encodes a protein comprising a mutation at an additional amino acid.

10. An adeno associated virus vector derived from the plasmid of claim 1 .

11. A method of delivering a polynucleotide that encodes a protein of interest to a tissue in a subject, the method comprising:
administering an effective amount of an adeno associated virus vector to the subject, wherein the adeno associated virus vector comprises an adeno associated virus plasmid comprising:
a polynucleotide that encodes a protein with the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least about 90% or at least about 95% sequence identity to SEQ ID NO: 1, wherein the protein further comprises a mutation at at least one of L380, T381, L382, N383, I440, D441, Y446, L447, T450, I451, V465, S469, N470, M471, Q474, G475, Y484, R485, E500, W503, P504, R514, N515, S516, and L517.

12. An adeno associated virus vector derived from the plasm id of claim 5 .

13. A method of delivering a polynucleotide that encodes a protein of interest to a tissue in a subject, the method comprising:
administering an effective amount of an adeno associated virus vector to the subject, wherein the adeno associated virus vector comprises an adeno associated virus plasmid comprising:
a polynucleotide that encodes a protein with the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence having at least about 90%, or at least about 95% sequence identity to SEQ ID NO: 4, the protein further comprises a mutation at at least one of Q464, A467, D469, I470, R471, D472, S474, S501, and D514.

14. An adeno associated virus plasmid comprising:
a polynucleotide that encodes a protein with the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence having at least about 60%, at least about 75%, at least about 80%, at least about 90%, or at least about 95% sequence identity to SEQ ID NO: 4, further comprising a Y500E mutation.

15. An adeno associated virus plasmid comprising:
a polynucleotide that encodes a protein with the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least about 60%, at least about 75%, at least about 80%, at least about 90%, or at least about 95% sequence identity to SEQ ID NO: 1, further comprising at least one of a F501A mutation, a G505A mutation, and a Q590A mutation.

Assignees

• Univ Oregon Health & Science
• Univ Pittsburgh Commonwealth Sys Higher Education

Inventors

• Nakai Hiroyuki
• Adachi Kei

Classifications

• C12N15/86 Primary

  Viral vectors · CPC title

• A61P43/00

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

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• C12N2750/14122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C12N2750/14141

  Use of virus, viral particle or viral elements as a vector · CPC title