Materials and methods for treatment of hemoglobinopathies
AssigneeVertex Pharmaceuticals Incorporated
InventorsTirtha Chakraborty, Bibhu Prasad Mishra, Chad Albert Cowan, Ante Sven Lundberg, Samarth Kulkarni, Todd Douglass Borland
Life of this patent
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Abstract
Provided are materials and methods for treating patients with hemoglobinopathies, either ex vivo or in vivo. Also provided are materials and methods for deleting and/or mutating a portion of a human beta globin locus on chromosome 11 and one or more of: a BCL11 A gene on chromosome 2, and a DNA sequence that encodes a transcriptional control region of the BCL11 A gene on chromosome 2, in a human cell by genome editing and thereby increasing the production of fetal hemoglobin (HbF) in the genome-edited human cells.
Claims18
An ex vivo or in vitro method of genome editing in a human cell comprising:
- introducing into the human cell one or more deoxyribonucleic acid (DNA) endonuclease and two or more guide ribonucleic acids (gRNAs) to effect
- (i) a first single-strand break (SSB) or double-strand break (DSB) within a human beta globin locus on chromosome 11;
- and
- (ii) a second SSB or DSB within a BCL11A gene on chromosome 2 or a DNA sequence that encodes a transcriptional control region of the BCL11A gene on chromosome 2;
- wherein the first SSB or DSB results in a permanent deletion or inversion within the human beta globin locus on chromosome 11 or a mutation within the human beta globin locus on chromosome 11;
- wherein the second SSB or DSB results in a permanent deletion or inversion within the BCL11A gene on chromosome 2, a mutation within the BCL11A gene on chromosome 2, a permanent deletion or inversion within the DNA sequence that encodes a transcriptional control region of the BCL11A gene on chromosome 2, or a mutation within the DNA sequence that encodes a transcriptional control region of the BCL11A gene on chromosome 2;
- and
- wherein the two or more gRNAs comprise at least two of the nucleic acid sequences of SEQ ID NOs:
- 228,428-228,436.
A method of treating a patient with a hemoglobinopathy by administering an edited autologous cell to the patient, wherein the edited cell has
- (i) a permanent deletion or inversion within the human beta globin locus on chromosome 11 or a mutation within the human beta globin locus on chromosome 11, and
- (ii) a permanent deletion or inversion within the BCL11A gene on chromosome 2,
- a mutation within the BCL11A gene on chromosome 2, a permanent deletion or inversion within the DNA sequence that encodes a transcriptional control region of the BCL11A gene on chromosome 2, or a mutation within the DNA sequence that encodes a transcriptional control region of the BCL11A gene on chromosome 2,
- wherein the deletions, inversions or mutations are made by two or more gRNAs, wherein the two or more gRNAs comprise at least two of the nucleic acid sequences of SEQ ID NOs:
- 228,428-228,436, wherein the deletions, inversions or mutations result in reduced expression of human beta globin and/or BCL11A in the edited cell.
Dependencies are inferred from the claim text.