Methods and compositions for treating Huntington's disease

• US 10,471,123 B2
• Filed: 03/04/2019
• Issued: 11/12/2019
• Est. Priority Date: 02/29/2012
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Therapeutics, Inc.
• Inventors: Miller, Jeffrey C., Rebar, Edward J., Zhang, H. Steve
• Primary Examiner(s): Weidner, Adam
• Application Number:
  US16/291,708
• Publication Number:
  US 20190183970A1
• Time in Patent Office: 253 Days
• Field of Search: None
• 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 compositions comprising non-naturally occurring zinc finger domains, fusion proteins comprising these zinc finger domains, polynucleotides encoding these proteins, cells expressing these proteins and pharmaceutical compositions comprising these proteins or polynucleotides as well as methods of modifying an Htt gene using these compositions for treating or preventing Huntington'"'"'s Disease.

Claims

1. A non-naturally occurring zinc finger protein comprising 6 zinc finger domains ordered F1 to F6, respectively, wherein the zinc finger protein specifically binds to mutant Huntington'"'"'s gene allele (mHtt) gene and comprises the recognition helix regions as follows:

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

3. A host cell comprising one or more zinc finger proteins of claim 1.

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

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

6. A method of modifying expression of an mHtt 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.

7. A polynucleotide encoding one or more fusion proteins according to claim 5.

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

9. A method of treating Huntington'"'"'s Disease, the method comprising administering one or more polynucleotides according to claim 7 to a subject in need thereof.

10. An AAV vector comprising the polynucleotide of claim 7.

11. The AAV vector of claim 10, wherein the AAV vector is an AAV6 or AAV9 vector.

12. A pharmaceutical composition comprising one or more AAV vectors according to claim 10.

13. A method of treating Huntington'"'"'s Disease, the method comprising administering one or more AAV vectors according to claim 10 to a subject in need thereof.