Engineered zinc finger proteins for treating trinucleotide repeat disorders

1. An engineered zinc finger protein that modulates expression of a gene associated with a trinucleotide repeat disorder, the zinc finger protein comprising 5 or 6 zinc finger recognition regions, ordered F1 to F5 or F1 to F6 from N-terminus to C-terminus, wherein the zinc finger protein comprises the recognition helix regions in the order shown in a single row of Table 1 and further wherein the zinc finger protein targets a sequence selected from the group consisting of SEQ ID NO:20-23 and 36-39.

2. The zinc finger protein of claim 1 , wherein the gene is wild-type.

3. The zinc finger protein of claim 2 , wherein the zinc finger protein binds to a SNP associated with a wild-type allele.

4. The zinc finger protein of claim 1 , wherein the gene comprises one or more expanded trinucleotide repeats.

5. The zinc finger protein of claim 4 , wherein the zinc finger protein binds to a SNP associated with the expanded trinucleotide repeat.

6. The zinc finger protein of claim 4 , wherein the expanded trinucleotide repeat encodes poly-glutamine.

7. The zinc finger protein of claim 4 , wherein the expanded trinucleotide repeat encodes poly-serine.

8. The zinc finger protein of claim 4 , wherein the expanded trinucleotide repeat is in a Huntington's Disease (HD) gene.

9. The zinc finger protein of claim 8 , wherein the HD gene is an Htt allele.

10. A multimer comprising at least two zinc fmger proteins of claim 1 , wherein the zinc finger proteins of the multimer preferentially bind to expanded trinucleotide tracts as compared to wild-type trinucleotide repeat tracts.

11. A pharmaceutical composition comprising a zinc finger protein of claim 1 .

12. An isolated cell comprising a zinc finger protein of claim 1 .

13. A polynucleotide encoding a zinc finger protein according to claim 1 .

14. An isolated cell comprising a polynucleotide according to claim 13 .

15. A pharmaceutical composition comprising a polynucleotide according to claim 13 .

16. A fusion protein comprising a zinc finger protein according to claim 1 and a regulatory domain, a cleavage domain or a cleavage half-domain.

17. The fusion protein of claim 16 , wherein the zinc finger protein activates expression of the gene.

18. The fusion protein of claim 16 , wherein the zinc finger protein represses expression of the gene.

19. A polynucleotide encoding a fusion protein according to claim 16 .