Compositions and methods to inhibit viral replication

Patent metadata

Field	Value
Publication number	US-10596234-B2
Application number	US-201715798388-A
Country	US
Kind code	B2
Filing date	Oct 30, 2017
Priority date	Oct 28, 2016
Publication date	Mar 24, 2020
Grant date	Mar 24, 2020

Abstract

This disclosure provides vaccine and therapeutic active against viral infections such as herpes simplex virus 1 (HSV-1) infections.

First claim

What is claimed is:

1. An isolated polynucleotide encoding a RIG-I-QQ mutant, complementary polynucleotides and equivalents of each thereof, wherein the encoded RIG-I-QQ mutant is a polypeptide that comprises the amino acid substitution(s) N495Q and/or N549Q according to SEQ ID NO:4.

2. An isolated polynucleotide encoding a RIG-I-QQ mutant polypeptide that has at least 90% sequence identity to SEQ ID NO: 4 while still comprising the amino acid substitution(s) N495Q and/or N549Q according to SEQ ID NO:4.

3. An isolated RIG-I-QQ mutant polypeptide that has at least 90% sequence identity to SEQ ID NO: 4 while still comprising the amino acid substitution(s) N495Q and/or N549Q according to SEQ ID NO:4.

4. The polynucleotide of claim 1 or 2 , further comprising a vector or gene delivery vehicle.

5. An isolated host cell comprising the isolated polynucleotide of claim 1 or 2 .

6. An isolated RIG-I-QQ mutant, wherein the RIG-I-QQ mutant comprises the amino acid substitution(s) N4950 and/or N549Q according to SEQ ID NO:4.

7. An isolated host cell comprising the polypeptide of claim 6 or 3 .

8. A composition comprising one or more of the polynucleotide of claim 1 or 2 , and a carrier.

9. A composition comprising the host cell of claim 7 and a carrier.

10. An isolated polypeptide encoded by the isolated polynucleotide of claim 1 or 2 .

11. An immunogenic composition comprising an effective amount of the isolated polypeptide of claim 6 or 3 and a pharmaceutically acceptable carrier.

12. The composition of claim 11 , further comprising an adjuvant.

13. An immunogenic composition comprising an effective amount of the isolated polynucleotide of claim 1 or 2 .

14. The composition of claim 13 , further comprising a carrier.

15. The composition of claim 14 , wherein the carrier is a pharmaceutically acceptable carrier and wherein the composition optionally further comprises an adjuvant.

16. A method comprising delivering an effective amount of the composition of claim 11 to a host, cell, or tissue.

17. The method of claim 16 , wherein the delivery can result in one or more of the following:
a) inhibiting viral replication;
b) abolishing 5′-ppp-RNA-binding and ATP hydrolysis;
c) switching off RIG-1;
d) blocking RNA-induced activation;
e) inhibiting the deamidation activity of herpes simplex virus (HSV) UL37;
f) inducing an anti-viral immune response;
g) inducing expression of anti-viral cytokine genes; or
h) enhancing the adaptive immune response in a host.

18. The method of claim 16 , wherein the delivery is in vivo or in vitro.

19. The method of claim 17 , wherein the delivery is in vivo or in vitro.

20. The method of claim 16 , wherein the host is a mammal or a human patient.

21. The method of claim 17 , wherein the host is a mammal or a human patient.

22. The method of claim 16 , wherein the delivery is in one or more doses.

23. The method of claim 17 , wherein the delivery is in one or more doses.

24. An isolated host cell comprising the isolated polynucleotide of claim 4 .

25. An immunogenic composition comprising an effective amount of the isolated polypeptide of claim 10 , a pharmaceutically acceptable carrier, and optionally an adjuvant.

26. An immunogenic composition comprising an effective amount of the isolated polynucleotide of claim 4 .

27. An isolated host cell comprising the polypeptide of claim 10 .

28. A composition comprising one or more of the polynucleotide of claim 4 and a carrier.

29. A method comprising delivering an effective amount of the composition of claim 13 to a host, cell, or tissue.

30. The method of claim 29 , wherein the delivery can result in one or more of the following:
a) inhibiting viral replication;
b) abolishing 5′-ppp-RNA-binding and ATP hydrolysis;
c) switching off RIG-1;
d) blocking RNA-induced activation;
e) inhibiting the deamidation activity of herpes simplex virus (HSV) UL37;
f) inducing an anti-viral immune response;
g) inducing expression of anti-viral cytokine genes; or
h) enhancing the adaptive immune response in a host.

31. The method of claim 29 , wherein the delivery is in vivo or in vitro.

32. The method of claim 30 , wherein the delivery is in vivo or in vitro.

33. The method of claim 29 , wherein the host is a mammal or a human patient.

34. The method of claim 30 , wherein the host is a mammal or a human patient.

35. The method of claim 29 , wherein the delivery is in one or more doses.

36. The method of claim 30 , wherein the delivery is in one or more doses.

Assignees

• Feng Pinghui
• Zhao Jun
• Univ Southern California

Inventors

• Feng Pinghui
• Zhao Jun

Classifications

• C12N9/14

  Hydrolases (3) · CPC title

• C12N2710/16663

  by chemical treatment · CPC title

• A61K38/46 Primary

  Hydrolases (3) · CPC title

• C12Y306/04013

  RNA helicase (3.6.4.13) · CPC title

• A61K47/646

  the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines · CPC title