DNA-binding proteins and uses thereof

Patent metadata

Field	Value
Publication number	US-10253333-B2
Application number	US-201715709969-A
Country	US
Kind code	B2
Filing date	Sep 20, 2017
Priority date	May 17, 2010
Publication date	Apr 9, 2019
Grant date	Apr 9, 2019

Abstract

Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.

First claim

The invention claimed is:

1. An isolated, non-naturally occurring TALE DNA-binding polypeptide comprising:
two or more TALE-repeat units, the TALE repeat units comprising a repeat variable di-residue (RVD); and wherein the N-terminal region lacks at least 152 amino acids of a full-length TALE protein and the C-terminal region is truncated to residue C+63, and further wherein the polypeptide binds to DNA.

2. The polypeptide of claim 1 , wherein at least one TALE-repeat unit comprises an atypical repeat variable di-residue (RVD).

3. The polypeptide of claim 2 , wherein the polypeptide comprises an atypical RVD as shown in Tables 27A or 27B.

4. The polypeptide of claim 1 , wherein the N-terminal region is truncated to residue N+134 to residue N+137.

5. The polypeptide of claim 1 , wherein the C-cap comprises a TALE repeat domain.

6. The polypeptide of claim 1 , further comprising a functional domain.

7. The polypeptide of claim 6 , wherein the functional domain is a transcriptional activator or a transcriptional repressor.

8. The polypeptide of claim 1 , wherein the functional domain comprises a nuclease domain.

9. The polypeptide of claim 8 , wherein the nuclease domain is an endonuclease domain.

10. An isolated cell comprising the polypeptide of claim 1 .

11. A pharmaceutical composition comprising the cell according to claim 10 .

12. A pharmaceutical composition comprising the polypeptide according to claim 1 .

Assignees

• Sangamo Therapeutics Inc

Inventors

• Gregory Philip D
• Miller Jeffrey C
• Paschon David
• Rebar Edward J
• Tan Siyuan
• Urnov Fyodor
• Zhang Lei

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title

• C12Y301/21004

  Type II site-specific deoxyribonuclease (3.1.21.4) · CPC title

• C12N15/52

  Genes encoding for enzymes or proenzymes · CPC title