Modulation of BCL11A for treatment of hemoglobinopathies
The invention relates to methods and uses of modulating fetal hemoglobin expression (HbF) in a hematopoietic progenitor cells via inhibitors of BCL11A expression or activity, such as RNAi and antibodies.
1. A CD34+ hematopoietic progenitor cell that comprises a vector encoding a nucleic acid that inhibits BCL11A expression.
2. The CD34+ hematopoietic progenitor cell of claim 1 , wherein the vector is a viral vector.
3. The CD34+ hematopoietic progenitor cell of claim 1 , wherein the viral vector is a lentiviral vector.
4. The CD34+ hematopoietic progenitor cell of claim 1 , wherein the nucleic acid is a BCL11A specific RNA interference agent.
5. The CD34+ hematopoietic progenitor cell of claim 4 , wherein the RNA interference agent comprises one or more of the nucleotide sequences set forth in SEQ ID NO:1-6.
6. The CD34+ hematopoietic progenitor cell of claim 1 , wherein the CD34+ hematopoietic progenitor cell is expanded ex vivo.
7. The CD34+ hematopoietic progenitor cell of any one of claims 1 to 6 , wherein the CD34+ hematopoietic progenitor cell is formulated for injection or infusion.
8. A composition comprising a CD34+ hematopoietic progenitor cell that comprises a viral vector encoding a nucleic acid that inhibits BCL11A expression.
9. The composition of claim 8 , wherein the viral vector is a lentiviral vector.
10. The composition of claim 8 , wherein the nucleic acid is a BCL11A specific RNA interference agent.
11. The composition of claim 10 , wherein the RNA interference agent comprises one or more of the nucleotide sequences set forth in SEQ ID NO:1-6.
12. The composition of claim 8 , wherein the composition further comprises a pharmaceutically acceptable carrier or diluent.
13. The composition of claim 8 , wherein the CD34+ hematopoietic progenitor cell is expanded ex vivo.
14. The composition of any one of claims 8 to 13 , wherein the CD34+ hematopoietic progenitor cell is formulated for injection or infusion.
15. A population of CD34+ hematopoietic progenitor cells, wherein the CD34+ hematopoietic progenitor cells comprise a viral vector encoding a nucleic acid that inhibits BCL11A expression.
16. The population of CD34+ hematopoietic progenitor cells of claim 15 , wherein the viral vector is a lentiviral vector.
17. The population of CD34+ hematopoietic progenitor cells of claim 15 , wherein the nucleic acid is a BCL11A specific RNA interference agent.
18. The population of CD34+ hematopoietic progenitor cells of claim 17 , wherein the RNA interference agent comprises one or more of the nucleotide sequences set forth in SEQ ID NO:1-6.
19. The population of CD34+ hematopoietic progenitor cells of claim 15 , wherein the CD34+ hematopoietic progenitor cells are expanded ex vivo.
20. The population of CD34+ hematopoietic progenitor cell of any one of claims 15 to 19 , wherein the CD34+ hematopoietic progenitor cells are formulated for injection or infusion.
21. A composition comprising a population of CD34+ hematopoietic progenitor cells that comprises a viral vector encoding a nucleic acid that inhibits BCL11A expression.
22. The composition of claim 21 , wherein the viral vector is a lentiviral vector.
23. The composition of claim 21 , wherein the nucleic acid is a BCL11A specific RNA interference agent.
24. The composition of claim 23 , wherein the RNA interference agent comprises one or more of the nucleotide sequences set forth in SEQ ID NO:1-6.
25. The composition of claim 21 , wherein the composition further comprises a pharmaceutically acceptable carrier or diluent.
26. The composition of claim 21 , wherein the CD34+ hematopoietic progenitor cells are expanded ex vivo.
27. The composition of any one of claims 21 to 26 , wherein the CD34+ hematopoietic progenitor cells are formulated for injection or infusion.