Methods of predicting ancestral virus sequences and uses thereof

Patent metadata

Field	Value
Publication number	US-2022017875-A1
Application number	US-202117408104-A
Country	US
Kind code	A1
Filing date	Aug 20, 2021
Priority date	Oct 11, 2013
Publication date	Jan 20, 2022
Grant date	—

Abstract

Methods are described for predicting ancestral sequences for viruses or portions thereof. Also described are predicted ancestral sequences for adeno-associated virus (AAV) capsid polypeptides. The disclosure also provides methods of gene transfer and methods of vaccinating subjects by administering a target antigen operably linked to the AAV capsid polypeptides.

First claim

1 - 9 . (canceled)

10 . A method comprising:
administering to a subject in need thereof a plurality of recombinant adeno-associated virus (rAAV) particles, wherein each rAAV particle comprises an AAV capsid polypeptide and a transgene, wherein the AAV capsid polypeptide comprises an amino acid sequence chosen from: SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, and 17, and the transgene is within the rAAV particle.

11 . The method of claim 10 , wherein the method is a method of vaccinating the subject.

12 . The method of claim 10 , wherein the method is a method of delivering a gene therapy to the subject.

13 . The method of claim 10 , wherein the AAV capsid polypeptide exhibits less seroprevalence than an AAV2 capsid polypeptide and/or about the same or less seroprevalence than an AAV8 capsid polypeptide.

14 . The method of claim 10 , wherein the AAV capsid polypeptide is neutralized to a lesser extent by human serum than an AAV2 capsid polypeptide, and wherein the AAV capsid polypeptide is neutralized to a similar or lesser extent by human serum than an AAV8 capsid polypeptide.

15 . The method of claim 10 , wherein the AAV capsid polypeptide has the sequence of SEQ ID NO: 1.

16 . A method comprising:
administering to a subject in need thereof a plurality of recombinant adeno-associated virus (rAAV) particles, wherein each rAAV particle comprises an AAV capsid polypeptide and a transgene, wherein the AAV capsid polypeptide comprises an amino acid sequence chosen from: SEQ ID NOs: 19, 20, 21, 22, 23, 24, 25, and 26, and the transgene is within the rAAV particle.

17 . The method of claim 16 , wherein the method is a method of vaccinating the subject.

18 . The method of claim 16 , wherein the method is a method of delivering a gene therapy to the subject.

19 . The method of claim 16 , wherein the AAV capsid polypeptide exhibits less seroprevalence than does an AAV2 capsid polypeptide and/or about the same or less seroprevalence than does an AAV8 capsid polypeptide.

20 . The method of claim 16 , wherein the AAV capsid polypeptide is neutralized to a lesser extent by human serum than is an AAV2 capsid polypeptide, and wherein the AAV capsid polypeptide is neutralized to a similar or lesser extent by human serum than is an AAV8 capsid polypeptide.

21 . The method of claim 16 , wherein the AAV capsid polypeptide has the sequence of SEQ ID NO: 23.

22 . The method of claim 10 , wherein the subject is a human.

23 . The method of claim 16 , wherein the subject is a human.

24 . The method of claim 10 , wherein the plurality of rAAV particles are in a composition further comprising a carrier.

25 . The method of claim 16 , wherein the plurality of rAAV particles are in a composition further comprising a carrier.

26 . The method of claim 10 , wherein the plurality of rAAV particles transduces or infects cells in the subject.

27 . The method of claim 26 , wherein the cells are ear cells.

28 . The method of claim 27 , wherein the ear cells are inner ear cells.

29 . The method of claim 16 , wherein the plurality of rAAV particles transduces or infects cells in the subject.

30 . The method of claim 29 , wherein the cells are ear cells.

31 . The method of claim 30 , wherein the ear cells are inner ear cells.

32 . The method of claim 13 , wherein the subject has a lower titer of antibodies that are capable of neutralizing the AAV capsid polypeptide than the titer of antibodies capable of neutralizing an AAV2 or AAV8 capsid polypeptide.

33 . The method of claim 19 , the subject has a lower titer of antibodies that are capable of neutralizing the AAV capsid polypeptide than the titer of antibodies capable of neutralizing an AAV2 or AAV8 capsid polypeptide.

Assignees

• Massachusetts Eye & Ear Infirmary
• Schepens Eye Res Inst

Inventors

• Vandenberghe Luk H
• Zinn Eric

Classifications

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• Y02A90/10

  Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation · CPC title

• C12N2750/14122

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

• C12N2750/14121

  Viruses as such, e.g. new isolates, mutants or their genomic sequences · CPC title

• A61P43/00

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