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 composition comprising a CD34+ hematopoietic progenitor cell that comprises a vector encoding a nucleic acid that inhibits BCL11A expression.
2. The composition of claim 1 , wherein the nucleic acid is a BCL11A specific RNA interference agent.
3. The composition of claim 2 , wherein the RNA interference agent comprises one or more of the nucleotide sequences set forth in SEQ ID NO:1-6.
4. The composition of claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier or diluent.
5. The composition of claim 1 , wherein the CD 34+ hematopoietic progenitor cell is expanded ex vivo.
6. The composition of claim 1 , wherein the CD 34+ hematopoietic progenitor cell is formulated for injection or infusion.
7. The composition of claim 2 , wherein the CD 34+ hematopoietic progenitor cell is formulated for injection or infusion.
8. The composition of claim 3 , wherein the CD 34+ hematopoietic progenitor cell is formulated for injection or infusion.
9. The composition of claim 4 , wherein the CD34+ hematopoietic progenitor cell is formulated for injection or infusion.
10. The composition of claim 5 , wherein the CD34+ hematopoietic progenitor cell is formulated for injection or infusion.
11. A population of CD34+ hematopoietic progenitor cells, wherein the CD 34+ hematopoietic progenitor cells comprise a vector encoding a nucleic acid that inhibits BCL11A expression.
12. The population of CD34+ hematopoietic progenitor cells of claim 11 , wherein the nucleic acid is a BCL11A specific RNA interference agent.
13. The population of CD34+ hematopoietic progenitor cells of claim 12 , wherein the RNA interference agent comprises one or more of the nucleotide sequences set forth in SEQ ID NO:1-6.
14. The population of CD34+ hematopoietic progenitor cells of claim 13 , wherein the CD 34+ hematopoietic progenitor cells are expanded ex vivo.