METHODS AND COMPOSITIONS FOR TREATING HUNTINGTON'S DISEASE

• US 20130253040A1
• Filed: 02/28/2013
• Published: 09/26/2013
• Est. Priority Date: 02/29/2012
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: C/O Sangamo Biosciences Incorporated
• Inventors: Miller, Jeffrey C., Rebar, Edward J., Zhang, H. Steve
• Granted Patent: US 8,841,260 B2
• Time in Patent Office: Days
• US Class Current: 514/44.R
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/70 containing domain for protein-protein interaction
• CPC Class Codes: C07K 2319/71 containing domain for transcriptional activaation, e.g. VP16
• CPC Class Codes: C07K 2319/81 containing a Zn-finger domain for DNA binding
• CPC Class Codes: C12N 15/907 in mammalian cells

Abstract

Disclosed herein are methods and compositions for treating or preventing Huntington'"'"'s Disease.

Claims

1. A non-naturally occurring zinc finger protein that binds to an Htt gene, the zinc finger protein comprising 4, 5 or 6 zinc finger domains ordered F1 to F4, F1 to F5 and F1 to F6, wherein the zinc finger domains comprise the recognition helix regions sequences shown in a single row of Table 1B.

2. The zinc finger protein of claim 1, wherein the zinc finger protein binds entirely or partially outside the CAG repeat region of the Htt gene.

3. The zinc finger protein of claim 1, wherein the zinc finger protein binds to sequences within the CAG repeat region of the Htt gene.

4. The zinc finger protein of claim 1, further comprising a dimerization domain that allows multimerization of zinc finger proteins when bound to DNA.

5. A fusion protein comprising a zinc finger protein of claim 1 and a functional domain.

6. The fusion protein of claim 5, wherein the functional domain is selected from the group consisting of a transcriptional activation domain, a transcriptional repression domain, and a nuclease domain.

7. A polynucleotide encoding one or more zinc finger proteins of claim 1.

8. A host cell comprising one or more zinc finger protein of claim 1.

9. A pharmaceutical composition comprising one or more zinc finger proteins according to claim 1.

10. A pharmaceutical composition comprising one or more polynucleotides according to claim 7.

11. A method of modifying expression of an Htt gene in a cell, the method comprising administering to the cell one or more polynucleotides encoding one or more fusion proteins according to claim 5.

12. The method of claim 11, wherein the Htt gene comprises at least one mutant allele.

13. The method of claim 11, wherein the Htt gene is wild-type.

14. The method of claim 11, wherein the fusion protein comprises a nuclease domain and expression of the Htt gene is inactivated.

15. A method of modifying an Htt gene in a cell, the method comprising, administering to the cell one or more polynucleotides encoding one or more fusion proteins according to claim 5, wherein the one or more fusion proteins comprises a nuclease domain and wherein the sequence of the Htt gene is modified.

16. A method of treating Huntington'"'"'s Disease, the method comprising administering to the cell one or more polynucleotides encoding one or more fusion proteins according to claim 5 to a subject in need thereof.

17. A method of generating a model system for the study of Huntington'"'"'s Disease, the method comprising modifying an Htt gene according to the method of claim 15.

18. The method of claim 17, wherein the Htt gene is modified to comprise one or more mutant alleles.

19. The method of claim 18, wherein the mutant alleles comprise expanded trinucleotide repeats.

20. The method of claim 17, wherein the cell comprises an embryonic stem cell.