Materials and Methods for Treatment of Human Genetic Diseases Including Hemoglobinopathies
AssigneeVertex Pharmaceuticals Incorporated
InventorMatthew Hebden Porteus
Life of this patent
Estimating the term…
Abstract
The present application provides materials and methods for treating hemoglobinopathies. More specifically, the application provides methods for producing progenitor cells that are genetically modified via genome editing to increase the production of fetal hemoglobin (HbF), as well as modified progenitor cells (including, for example, CD34+ human hematopoietic stem cells) producing increased levels of HbF, and methods of using such cells for treating hemoglobinopathies such as sickle cell anemia and β-thalassemia.
Claims28
A method of increasing the level of fetal hemoglobin (HbF) in a human cell by genome editing, the method comprising introducing Cas9 endonuclease, a first guide RNA (gRNA), and a second gRNA into a human cell to effect a pair of double-strand breaks (DSBs) within the S8-globin region of human chromosome 11, wherein the first gRNA comprises a spacer sequence that hybridizes to the same target sequence of the δβ-globin region of human chromosome 11 as a nucleic acid having the nucleic acid sequence of any one of SEQ ID NO:
- 1-117 and 129-137, the second gRNA comprises a spacer sequence that hybridizes to the same target sequence of the δβ-globin region of human chromosome 11 as a nucleic acid having the nucleic acid sequence of any one of SEQ ID NO:
- 1-117 and 129-137, wherein the first gRNA hybridizes to a different target sequence than the second gRNA, wherein the editing results in increased expression of γ-globin, thereby increasing the level of HbF in the cell.
(canceled)
5-6. (canceled)
8-9. (canceled)
12-13. (canceled)
15-28. (canceled)
33-47. (canceled)
(canceled)
55-71. (canceled)
A method of ameliorating a β-hemoglobinopathy in human patient comprising administering to such patient a human cell, wherein the human cell has been modified by introducing into the cell Cas9 endonuclease, a first guide RNA (gRNA), and a second gRNA to effect a pair of double-strand breaks (DSBs) within the δβ-globin region of human chromosome 11, wherein the first gRNA comprises a spacer sequence that hybridizes to the same target sequence of the δβ-globin region of human chromosome 11 as a nucleic acid having the nucleic acid sequence of any one of SEQ ID NO:
- 1-117 and 129-137, the second gRNA comprises a spacer sequence that hybridizes to the same target sequence of the δβ-globin region of human chromosome 11 as a nucleic acid having the nucleic acid sequence of any one of SEQ ID NO:
- 1-117 and 129-137, wherein the first gRNA hybridizes to a different target sequence than the second gRNA, wherein the editing results in increased expression of HbF in the cell.
Dependencies are inferred from the claim text.