Htt repressors and uses thereof

1. A cell comprising a non-naturally occurring zinc finger protein transcription factor (ZFP-TF) that represses expression of mutant human or mouse Huntingtin (Htt) gene (mHtt), the zinc finger protein transcription factor comprising:

(a) a transcriptional repression domain; and

(b) a zinc finger protein designated SBS #45643 or SBS #46025, the zinc finger protein comprising 5 zinc finger domains ordered F1 to F5 as follows:

(i)

F1:

(SEQ ID NO: 1)

QSGDLTR;

F2:

(SEQ ID NO: 1)

QSGDLTR;

F3:

(SEQ ID NO: 1)

QSGDLTR;

F4:

(SEQ ID NO: 2)

KHGNLSE;

and

F5:

(SEQ ID NO: 3)

KRCNLRC;

or

(ii)

F1:

(SEQ ID NO: 4)

CPSHLTR;

F2:

(SEQ ID NO: 1)

QSGDLTR;

F3:

(SEQ ID NO: 2)

KHGNLSE;

F4:

(SEQ ID NO: 3)

KRCNLRC;

and

F5:

(SEQ ID NO: 5)

RQFNRHQ.

2. The cell of claim 1 , comprising a polynucleotide encoding one or more zinc finger protein-transcription factors.

3. The cell of claim 2 , wherein the polynucleotide is carried by an AAV vector.

4. The cell of claim 1 , wherein the cell is a fibroblast or a neuron.

5. A method of rescuing a cellular phenotype in an HD neuron comprising a mutant Htt gene having at least 35 expanded CAG repeats, the method comprising bilaterally injecting into the striatum of a mouse or human an adeno-associated virus (AAV) vector comprising a sequence encoding a non-naturally occurring zinc finger protein transcription factor (ZFP-TF) that represses expression of mutant human or mouse Htt gene (mHtt) in the HD neuron, the zinc finger protein transcription factor comprising:

(a) a transcriptional repression domain comprising a Krüppel associated box (KRAB) domain; and

(b) a zinc finger protein designated SBS #45643 or SBS #46025, the zinc finger protein comprising 5 zinc finger domains ordered F1 to F5 as follows:

(i)

F1:

(SEQ ID NO: 1)

QSGDLTR;

F2:

(SEQ ID NO: 1)

QSGDLTR;

F3:

(SEQ ID NO: 1)

QSGDLTR;

F4:

(SEQ ID NO: 2)

KHGNLSE;

and

F5:

(SEQ ID NO: 3)

KRCNLRC;

or

(ii)

F1:

(SEQ ID NO: 4)

CPSHLTR;

F2:

(SEQ ID NO: 1)

QSGDLTR;

F3:

(SEQ ID NO: 2)

KHGNLSE;

F4:

(SEQ ID NO: 3)

KRCNLRC;

and

F5:

(SEQ ID NO: 5)

RQFNRHQ.

6. The method of claim 5 , wherein the rescued cellular phenotype is selected from the group consisting of decreasing cell death, increasing cell function and decreasing cell susceptibility to apoptosis.

7. The method of claim 6 , wherein ATP levels in the HD neuron are increased.

8. The method of claim 7 , wherein susceptibility to apoptosis in the HD neuron is reduced.

9. The method of claim 5 , wherein Huntington's disease is treated and/or prevented in the mouse or human following bilateral injection of said AAV vector.