Methods and compositions for treatment of a genetic condition

• US 9,902,974 B2
• Filed: 12/10/2015
• Issued: 02/27/2018
• Est. Priority Date: 05/15/2013
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Therapeutics, Inc.
• Inventors: Conway, Anthony, Cost, Gregory J., DeKelver, Russell, Rebar, Edward J., Reik, Andreas, Urnov, Fyodor, Wang, Jianbin, Zhang, H. Steve
• Primary Examiner(s): GALISTEO GONZALE, ANTONIO
• Application Number:
  US14/965,629
• Publication Number:
  US 20160090607A1
• Time in Patent Office: 810 Days
• Field of Search: None
• CPC Class Codes: C07K 14/805 Haemoglobins; Myoglobins
• CPC Class Codes: C07K 2/00 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: C07K 2319/81 containing a Zn-finger domain for DNA binding
• CPC Class Codes: C12N 15/11 DNA or RNA fragments; Modified forms thereof DNA or RNA not used in recombinant technology, C07H21/00; Non-coding nucleic acids having a biological activity
• CPC Class Codes: C12N 15/63 Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• CPC Class Codes: C12N 15/90 Stable introduction of foreign DNA into chromosome
• CPC Class Codes: C12N 15/902 using homologous recombination
• CPC Class Codes: C12N 15/907 in mammalian cells
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: C12N 9/22 Ribonucleases RNAses, DNAses catalytic nucleic acids C12N15/113
• CPC Class Codes: C12Y 301/21004 Type II site-specific deoxyribonuclease (3.1.21.4)

Abstract

Methods and compositions comprising a fusion protein comprising a Cas protein and a functional domain in association with a single guide RNA targeted to an endogenous gene for genetic alteration of cells are provided.

Claims

1. A fusion protein comprising a Cas protein and a functional domain in association with a single-guide RNA comprising a sequence selected from the group consisting of SEQ ID NOs:

149-158 and 167-215.

2. The fusion protein of claim 1, wherein the functional domain is a transcriptional activation domain, a transcriptional repression domain or a nuclease domain.

3. The fusion protein of claim 2, wherein the nuclease domain is a FokI endonuclease domain.

4. The fusion protein of claim 3, wherein the FokI endonuclease domain comprises one or more mutations in the dimerization domain.

5. A dimer comprising first and second fusion proteins according to claim 3.

6. The dimer of claim 5, wherein the first fusion protein comprises a FokI endonuclease domain comprising one or more mutations in the catalytic domain.

7. A pharmaceutical composition comprising a fusion protein according to claim 1.