METHODS AND COMPOSITIONS FOR TREATMENT OF A GENETIC CONDITION

• US 20140080216A1
• Filed: 08/29/2013
• Published: 03/20/2014
• Est. Priority Date: 08/29/2012
• Status: Active Grant

• Current Assignee: Sangamo Therapeutics, Inc.
• Original Assignee: Sangamo Biosciences, Inc. (Sangamo Therapeutics, Inc.)
• Inventors: Cost, Gregory J., Gregory, Philip D., Guschin, Dmitry, Holmes, Michael C., Miller, Jeffrey C., Rebar, Edward J., Urnov, Fyodor, Paschon, David, Reik, Andreas, Zhang, Lei
• Granted Patent: US 9,650,648 B2
• Time in Patent Office: Days
• US Class Current: 435/462
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C07K 14/805 Haemoglobins; Myoglobins
• CPC Class Codes: C07K 2319/81 containing a Zn-finger domain for DNA binding
• CPC Class Codes: C12N 15/52 Genes encoding for enzymes or proenzymes
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 9/22 Ribonucleases RNAses, DNAses catalytic nucleic acids C12N15/113

Abstract

Methods and compositions for a genetic disease are provided.

Claims

1. A non-naturally occurring fusion protein comprising a TALE DNA binding domain that binds to an endogenous BCL11A, KLF1 or globin gene and a cleavage domain, wherein the fusion protein modifies the endogenous BCL11A, KLF1 or globin gene.

2. The fusion protein of claim 1, wherein the TALE DNA binding protein binds to a sequence as shown in a single row of Table 1C or Table 3.

3. The fusion protein of claim 1 wherein the cleavage domain or cleavage half-domain is a wild-type domain.

4. The fusion protein of claim 1, wherein the cleavage domain or cleavage half-domain is an engineered domain.

5. A polynucleotide encoding one or more proteins of claim 1.

6. An isolated cell comprising one or more fusion proteins according to claim 1.

7. An isolated cell comprising one or more polynucleotides according to claim 5.

8. The cell of claim 7, wherein the cell is a red blood cell (RBC) precursor cell.

9. The cell of claim 6 wherein the cell is a red blood cell (RBC).

10. The cell of claim 8, wherein the RBC precursor cell is a CD34+ hematopoietic stem cell.

11. A kit comprising a protein according to claim 1.

12. A kit comprising a polynucleotide according to claim 5.

13. A method of altering globin gene expression in a cell, the method comprising:

introducing, into the cell, one or more polynucleotides according to claim 5, under conditions such that the one or more proteins are expressed and expression of the globin gene is altered.

14. The method of claim 13, wherein the proteins increase expression of a globin gene.

15. The method of claim 14, wherein the globin gene is a gamma globin or beta globin gene.

16. The method of claim 13, further comprising integrating a donor sequence into the genome of the cell.

17. The method of claim 16, wherein the donor sequence is introduced to the cell using a viral vector, as an oligonucleotide or on a plasmid.

18. The method of claim 13, wherein the cell is a red blood cell (RBC) precursor cell or a hematopoietic stem cell.

19. The cell of claim 18, wherein the hematopoietic stem cell is a CD34+ stem cell.

20. The method of claim 16, wherein the donor sequence comprises a transgene under the control of an endogenous promoter.

21. The method of claim 16, wherein the donor sequence comprises a transgene under the control of an exogenous promoter.