HTT repressors and uses thereof

• US 10,435,441 B2
• Filed: 09/23/2016
• Issued: 10/08/2019
• Est. Priority Date: 09/23/2015
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Therapeutics, Inc.
• Inventors: Froelich, Steven, Miller, Jeffrey C., Paschon, David, Rebar, Edward J., Zeitler, Bryan, Zhang, H. Steve
• Primary Examiner(s): Wehbe, Anne Marie S
• Application Number:
  US15/274,357
• Publication Number:
  US 20170096460A1
• Time in Patent Office: 1,110 Days
• Field of Search: 530350, 514 44 R
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C07K 2319/81 containing a Zn-finger domain for DNA binding
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 15/8645 Adeno-associated virus
• CPC Class Codes: C12N 5/0619 Neurons
• CPC Class Codes: C12N 5/0656 Adult fibroblasts
• CPC Class Codes: C12N 5/10 Cells modified by introduction of foreign genetic material

Abstract

Disclosed herein are Htt repressors and methods and compositions for use of these Htt repressors.

Claims

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.