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Title: | Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia |
Authors: | Mettananda, S. Fisher, C.A. Hay, D. Badat, M. Quek, L. Clark, K. Hublitz, P. Downes, D. Kerry, J. Gosden, M. Telenius, J. Sloane-Stanley, J.A. Faustino, P. Coelho, A. Doondeea, J. Usukhbayar, B. Sopp, P. Sharpe, J.A. Hughes, J.R. Vyas, P. Gibbons, R.J. Higgs, D.R. |
Keywords: | β-Thalassemia |
Issue Date: | 2017 |
Publisher: | Nature Pub. Group |
Citation: | Nature Communications.2017;8(1):424 |
Abstract: | β-Thalassemia is one of the most common inherited anemias, with no effective cure for most patients. The pathophysiology reflects an imbalance between α- and β-globin chains with an excess of free α-globin chains causing ineffective erythropoiesis and hemolysis. When α-thalassemia is co-inherited with β-thalassemia, excess free α-globin chains are reduced significantly ameliorating the clinical severity. Here we demonstrate the use of CRISPR/Cas9 genome editing of primary human hematopoietic stem/progenitor (CD34+) cells to emulate a natural mutation, which deletes the MCS-R2 α-globin enhancer and causes α-thalassemia. When edited CD34+ cells are differentiated into erythroid cells, we observe the expected reduction in α-globin expression and a correction of the pathologic globin chain imbalance in cells from patients with β-thalassemia. Xenograft assays show that a proportion of the edited CD34+ cells are long-term repopulating hematopoietic stem cells, demonstrating the potential of this approach for translation into a therapy for β-thalassemia.β-thalassemia is characterised by the presence of an excess of α-globin chains, which contribute to erythrocyte pathology. Here the authors use CRISP/Cas9 to reduce α-globin expression in hematopoietic precursors, and show effectiveness in xenograft assays in mice. |
Description: | Indexed In MEDLINE |
URI: | http://repository.kln.ac.lk/handle/123456789/17708 |
ISSN: | 2041-1723 (Electronic) 2041-1723 (Linking) |
Appears in Collections: | Journal/Magazine Articles |
Files in This Item:
File | Description | Size | Format | |
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betaThalasemia.2017.pdf | 2.7 MB | Adobe PDF | View/Open |
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