Small Interfering RNAs Targeting Feline Herpes Virus

• US 20090203138A1
• Filed: 02/12/2009
• Published: 08/13/2009
• Est. Priority Date: 02/12/2008
• Status: Active Grant

• Current Assignee: University of Tennessee Research Foundation (University of Teesside)
• Original Assignee: University of Tennessee Research Foundation (University of Teesside)
• Inventors: Kania, Stephen A., Wilkes, Rebecca P.
• Granted Patent: US 7,977,321 B2
• Time in Patent Office: Days
• US Class Current: 435/375
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: C12N 15/1133 against herpetoviridae, e.g. HSV
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2320/31 Combination therapy

Abstract

The present application provides polynucleotides, compositions thereof and methods of treating feline herpes virus infections. In certain embodiments, the polynucleotides and compositions thereof can be used to reduce replication of feline herpes simplex virus 1 (FHV-1) in vivo and/or in vitro.

Claims

1. A composition comprising a carrier and a combination of two or more polynucleotides selected from SEQ ID NOs:

7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17.

2. The composition of claim 1, wherein said combination of two or more polynucleotides are those set forth in Table 5.

3. The composition of claim 2, wherein said combination of two or more polynucleotides are double stranded siRNA molecules of between 16 and 30 nucletotides, said double stranded siRNA molecules comprising a first sequence comprising SEQ ID NO:

7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17 and a second sequence that is complementary thereto, wherein said siRNA molecule contains 0, 1, 2, 3 or 4 base mismatches.

4. The composition of claim 3, wherein said combination of nucleotides are SEQ ID NOs:

7 and 9 or SEQ ID NOs;

7 and 12.

17. The method of claim 16, wherein said composition is a composition according to claim 1.

5. An isolated polynucleotide that reduces expression of feline glyceraldehyde-3-phosphate dehydrogenase (GAPDH), FHV-1 DNA polymerase or glycoprotein D polypeptides, wherein said polynucleotide is selected from an interfering RNA that targets:

a) nucleotides 624-606, 679-661 or 785-767 of the GAPDH gene set forth in GenBank Accession No. AB038241 [SEQ ID NO;

1];

b) nucleotides 23-5, 70-52, 95-77, 121-103 or 144-126 of the FHV-1 polymerase gene set forth in GenBank Accession No. AF079125 [SEQ ID NO;

2];

c) nucleotides 1076-1058, 1351-1333, 1397-1379, 1556-1538 or 1591-1573 of the FHV-1 glycoprotein D gene set forth in GenBank Accession No. D30767 [SEQ ID NO;

3];

or

d) SEQ ID NO;

39.

6. The polynucleotide of claim 5, wherein said polynucleotide comprises SEQ ID NO:

4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17.

7. The polynucleotide of claim 5, wherein said polynucleotide is an siRNA or a shRNA.

8. A composition comprising a polynucleotide according to claim 5 and a pharmaceutically acceptable carrier.

9. The composition according to claim 8, wherein said polynucleotide is an siRNA or a shRNA.

10. A composition comprising a pharmaceutically acceptable carrier and a combination of two or more polynucleotides according to claim 5.

11. A method of decreasing expression of FHV-1 DNA polymerase and/or glycoprotein D in cells, comprising administering a composition comprising an effective amount of a polynucleotide that reduces expression of FHV-1 DNA polymerase and/or glycoprotein D.

12. The method of claim 11, wherein said polynucleotide is an interfering RNA, anti-sense oligonucleotide, or ribozyme.

13. The method of claim 11, wherein said polynucleotide is selected from an interfering RNA that targets:

a) nucleotides 23-5, 70-52, 95-77, 121-103 or 144-126 of the FHV-1 polymerase gene set forth in GenBank Accession No. AF079125 [SEQ ID NO;

2];

or

b) nucleotides 1076-1058, 1351-1333, 1397-1379, 1556-1538 or 1591-1573 of the FHV-1 glycoprotein D gene set forth in GenBank Accession No. D30767 [SEQ ID NO;

3].

14. The method of claim 11, wherein said polynucleotide comprises SEQ ID NO:

7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17.

15. The method of claim 11, wherein said composition comprises a combination of two or more polynucleotides is selected from SEQ ID NOs:

7, 8, 9, 10, 11, 12, 13, 14, 15, 16 or 17.

16. The method of claim 11, wherein said composition is administered to a mucosal surface of a feline.

18. The method of claim 16, wherein said composition is a composition according to claim 2.

19. The method of claim 16, wherein said composition is a composition according to claim 3.

20. The method of claim 16, wherein said composition is a composition according to claim 4.