Methods and compositions for dual glycan binding aav vectors

Patent metadata

Field	Value
Publication number	US-2018371024-A1
Application number	US-201816110773-A
Country	US
Kind code	A1
Filing date	Aug 23, 2018
Priority date	Mar 15, 2013
Publication date	Dec 27, 2018
Grant date	—

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

1 . (canceled)

2 . An adeno-associated virus (AAV) capsid protein, comprising the following amino acids substitutions:
a) a substitution corresponding to A266S of AAV2; b) substitutions corresponding to amino acids 463-475 of SQAGASDIRDQSR463-475SVAGPSNMAVQGR of AAV2; and c) substitutions corresponding to amino acids 499-502 of EYSW499-502EFAW of AAV2;
wherein the substitutions introduce a galactose binding site from donor AAV9 serotype into the capsid protein of a template recipient AAV serotype.

3 . The adeno-associated virus (AAV) capsid protein of claim 2 , wherein the recipient AAV serotype is selected from the group consisting of human AAV and non-human AAV.

4 . The adeno-associated virus (AAV) capsid protein of claim 3 , wherein the recipient AAV serotype is selected from the group consisting of human AAV, non-human primate AAV, avian AAV, and bovine AAV.

5 . The adeno-associated virus (AAV) capsid protein of claim 2 , wherein the recipient AAV serotype is selected from the group consisting of AAV1, AAV2, AAV3a, AAV3b, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, Avian AAV, BB1, BB2, CH5, CY2, CY3, CY4, CY5, CY6, Hu LG15, Hu S17, Hu T17, Hu T41, Hu T70, Hu T71, Hu T88, Hu1, Hu2, Hu3, Hu4, Hu6, Hu7, Hu9, Hu10, Hu11, Hu13, Hu15, Hu16, Hu17, Hu18, Hu19, Hu20, Hu21, Hu22, Hu23, Hu24, Hu25, Hu27, Hu28, Hu29, Hu34, Hu35, Hu37, Hu39, Hu40, Hu41, Hu42, Hu43, Hu44, Hu45, Hu46, Hu47, Hu48, Hu49, Hu51, Hu52, Hu54 Hu55, Hu56, Hu57, Hu58, Hu60, Hu61, Hu63, Hu64, Hu66, Hu67, Rh1, Rh2, Rh8, Rh10, Rh12, Rh13, Rh14, Rh16, Rh17, Rh18, Rh19, Rh22, Rh23, Rh24, Rh25, Rh26, Rh27, Rh31, Rh32, Rh33, Rh34, Rh35, Rh36, Rh37, Rh38, Rh40, Rh43, Rh48, Rh49, Rh50, Rh51, Rh52, Rh53, Rh54, Rh55, Rh57, Rh58, Rh60, Rh61, Rh62, and Rh64.

6 . The adeno-associated virus (AAV) capsid protein of claim 5 , wherein the recipient AAV serotype is selected from the group consisting of AAV1, AAV2, AAV3a, AAV3b, AAV4, AAV5, AAV6, AAV7, AAV8 and AAV10.

7 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV1 and the corresponding amino acid substitutions are A267S, SRGSPAGMSVQPK464-476SVAGPSNMAVQGR, and NFTW500-503EFAW.

8 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV2.

9 . The AAV capsid protein of claim 8 , wherein amino acids 585-590 are further substituted with QQNTAP.

10 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV3a and the corresponding amino acid substitutions are A266S, SQAGPQSMSLQAR464-476SVAGPSNMAVQGR, and NFPW500-503EFAW.

11 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV3b and the corresponding amino acid substitutions are A266S, SQAGPQSMSLQAR464-476SVAGPSNMAVQGR, and NFPW500-503EFAW.

12 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV4 and the corresponding amino acid substitutions are insert SSND before N261, TKLRPTNFSNFKK458-470SVAGPSNMAVQGR, and DSLI499-502EFAW.

13 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV5 and the corresponding amino acid substitutions are G257S, NKNLAGRYANTYK450-463SVAGPSNMAVQGR, and VSAF486-489EFAW.

14 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV6 and the corresponding amino acid substitutions are A267S, SRGSPAGMSVQPK464-476SVAGPSNMAVQGR, and NFTW500-503EFAW.

15 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV7 and the corresponding amino acid substitutions are VQGGPSTMAEQAK466-478SVAGPSNMAVQGR, and NFAW502-505EFAW.

16 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV8 and the corresponding amino acid substitutions are A269S, SQGGPNTNANQAK466-478SVAGPSNMAVQGR, and NFAW502-505EFAW.

17 . The AAV capsid protein of claim 5 , wherein the recipient serotype is AAV10 and the corresponding amino acid substitutions are T270S, SQAGPANMSAQAK466-478SVAGPSNMAVQGR, and N502E.

18 . An AAV capsid comprising the AAV capsid protein of claim 2 .

19 . A virus vector comprising:
(a) the AAV capsid of claim 18 ; and (b) a nucleic acid comprising at least one terminal repeat sequence, wherein the nucleic acid is encapsidated by the AAV capsid.

20 . A composition comprising the AAV capsid protein of claim 2 in a pharmaceutically acceptable carrier.

21 . A composition comprising the AAV capsid of claim 17 in a pharmaceutically acceptable carrier.

22 . A composition comprising the virus vector of claim 18 in a pharmaceutically acceptable carrier

23 . A method of introducing a nucleic acid into a cell, comprising contacting the cell with the virus vector of claim 19 .

24 . The method of claim 23 , wherein the cell is in a subject.

25 . The method of claim 24 , 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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P31/14

  for RNA viruses · CPC title

• A61P31/22

  for herpes viruses · CPC title