Methods and sequences to suppress primate Huntington gene expression
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.
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 SEQ ID NO: 8, and the second strand is complementary to at least 15 contiguous nucleotides within said at least 19 contiguous nucleotides of SEQ ID NO: 8 of the first strand.
2. The isolated nucleic acid duplex of claim 1 , wherein the first strand is connected to the second strand by means of a loop.
3. The isolated nucleic acid duplex of claim 1 , wherein the second strand is complementary to 19 nucleotides within SEQ ID NO: 8 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.
12. The isolated nucleic acid duplex of claim 1 , wherein the nucleic acid duplex is between 19 and 30 base pairs in length.
13. The isolated nucleic acid duplex of claim 12 , wherein the first strand is connected to the second strand by means of a loop.
14. The isolated nucleic acid duplex of claim 12 , wherein the second strand is complementary to 19 nucleotides within SEQ ID NO: 8 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.
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.