METHODS AND SEQUENCES TO SUPPRESS PRIMATE HUNTINGTON GENE EXPRESSION

• US 20100008981A1
• Filed: 09/10/2009
• Published: 01/14/2010
• Est. Priority Date: 05/06/2005
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Kaemmerer, William F., Kaytor, Michael D.
• Granted Patent: US 8,258,112 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/14 interfering N.A.

Abstract

Disclosed herein are sequences, molecules and methods used to suppress the expression of HD genes encoding for huntingtin protein in primates including Macaca mulatto and Homo sapiens. These sequences, molecules and methods aid in the study of the pathogenesis of HD and can also provide a treatment for this disease.

Claims

1. An isolated nucleic acid duplex comprising a first strand of nucleic acid and a second strand of nucleic acid, wherein

the first strand comprises at least 19 contiguous nucleotides encoded by one of SEQ ID NOs:

7, 8, 6, 2, 3, or 5, and

the second strand is complementary to at least 15 contiguous nucleotides within a respective SEQ ID NO;

7, 8, 6, 2, 3, or 5 of the first strand.

2. The isolated nucleic acid duplex of claim 1, wherein the first strand is connected to the second strand my means of a loop.

3. The isolated nucleic acid duplex of claim 1, wherein the second strand is complementary to 19 nucleotides within the respective SEQ ID NO:

7, 8, 6, 2, 3, or 5 of the first strand.

4. A vector encoding the isolated nucleic acid duplex of claim 1.

5. The vector of claim 4, wherein the vector is a viral vector.

6. The vector of claim 5, wherein the viral vector is an adeno-associated viral vector.

7. A method for suppression of huntingtin in a cell comprising administering to the cell an isolated nucleic acid duplex of claim 1.

8. The method according to claim 7, wherein the cell is within a mammalian patient.

9. The method according to claim 8, wherein said mammalian patient is a human patient.

10. The method according to claim 7, wherein the nucleic acid duplex of claim 1 is within a vector.

11. The method of claim 10, wherein said vector is complexed with cationic lipids or packaged within liposomes microparticles, or microcapsules.

21. The method according to claim 18, wherein the nucleic acid duplex of claim 1 is within a vector.

22. The method of claim 21, wherein said vector is complexed with cationic lipids or packaged within liposomes microparticles, or microcapsules.

12. An isolated nucleic acid duplex comprising a first strand of nucleic acid and a second strand of nucleic acid, wherein

the first strand comprises at least 19 contiguous nucleotides encoded by one of SEQ ID NOs:

7, 8, 6, 3, or 5, and

the second strand is complementary to at least 15 contiguous nucleotides within a respective SEQ ID NO;

7, 8, 6, 3, or 5 of the first strand.

13. The isolated nucleic acid duplex of claim 12, wherein the first strand is connected to the second strand my means of a loop.

14. The isolated nucleic acid duplex of claim 12, wherein the second strand is complementary to 19 nucleotides within the respective SEQ ID NO:

7, 8, 6, 3, or 5 of the first strand.

15. A vector encoding the isolated nucleic acid duplex of claim 12.

16. The vector of claim 15, wherein the vector is a viral vector.

17. The vector of claim 16, wherein the viral vector is an adeno-associated viral vector.

18. A method for suppression of huntingtin in a cell comprising administering to the cell an isolated nucleic acid duplex of claim 12.

19. The method according to claim 18, wherein the cell is within a mammalian patient.

20. The method according to claim 19, wherein said mammalian patient is a human patient.