HTT repressors and uses thereof
Disclosed herein are Htt repressors and methods and compositions for use of these Htt repressors.
1. A non-naturally occurring zinc finger protein transcription factor (ZFP-TF) that represses expression of mutant human or mouse 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: QSGDLTR (SEQ ID NO:1);
F2: QSGDLTR (SEQ ID NO:1);
F3: QSGDLTR (SEQ ID NO:1);
F4: KHGNLSE (SEQ ID NO:2); and
F5: KRCNLRC (SEQ ID NO:3); or
(ii) F1: CPSHLTR (SEQ ID NO:4);
F2: QSGDLTR (SEQ ID NO:1);
F3: KHGNLSE (SEQ ID NO:2);
F4: KRCNLRC (SEQ ID NO:3); and
F5: RQFNRHQ (SEQ ID NO:5).
2. A polynucleotide encoding one or more zinc finger protein transcription factors of claim 1 .
3. An AAV vector comprising the polynucleotide of claim 2 .
4. A host cell comprising one or more zinc finger protein transcription factors of claim 1 .
5. A pharmaceutical composition comprising one or more AAV vectors according to claim 3 .
6. A method of repressing expression of a mutant Htt gene in a neuronal cell in a brain, the method comprising intrastriatally administering to the cell one or more polynucleotides according to claim 2 .
7. A method of treating and/or preventing Huntington's Disease in a subject in need thereof, the method comprising administering one or more AAV vectors according to claim 3 into the striatum of the subject in need thereof.