Targeting BCL11A distal regulatory elements for fetal hemoglobin reinduction
AssigneeChildren's Medical Center Corporation
InventorsStuart H. Orkin, Daniel E. Bauer, Jian Xu
Life of this patent
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Abstract
Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.
Claims14
A human hematopoietic progenitor cell comprising at least one genetic modification within chromosome 2 between positions 60,716,189 and 60,728,612 (according to UCSC Genome Browser hg 1.9 human genome assembly),
- wherein the human hematopoietic progenitor cell comprises i) a vector comprising a regulatory element operably linked to a coding sequence of a DNA-targeting endonuclease comprising a TAL DNA binding domain or ii) an RNA encoding a DNA-targeting endonuclease comprising a TAL DNA binding domain;
- wherein the DNA-targeting endonuclease binds to and cleaves the genomic DNA of the cell within the chromosome 2 between positions 60,716,189 and 60,728,612 to generate the at least one genetic modification;
- wherein the at least one genetic modification is an insertion or a deletion that disrupts DNAse hypersensitive sites +62, +58, or +55 therein;
- and
- wherein the at least one genetic modification reduces BCL11A mRNA and protein expression in the human hematopoietic progenitor cell or its progeny.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a human hematopoietic progenitor cell comprising at least one genetic modification within chromosome 2 between positions 60,716,18960,728,612 (according to UCSC Genome Browser hg 1.9 human genome assembly), wherein the at least one genetic modification is an insertion or a deletion that disrupts DNAse hypersensitive sites +62, +58, or +55 therein, and wherein the at least one genetic modification reduces BCL11A mRNA and protein expression in the human hematopoietic progenitor cell or its progeny.
Dependencies are inferred from the claim text.