Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia

Sachith Mettananda, Chris A. Fisher, Deborah Hay, Mohsin Badat, Lynn Quek, Kevin Clark, Philip Hublitz, Damien Downes, Jon Kerry, Matthew Gosden, Jelena Telenius, Jackie A. Sloane-Stanley, Paula Faustino, Andreia Coelho, Jessica Doondeea, Batchimeg Usukhbayar, Paul Sopp, Jacqueline A. Sharpe, Jim R. Hughes, Paresh Vyas, Richard J. Gibbons and Douglas R. Higgs ()
Additional contact information
Sachith Mettananda: University of Oxford
Chris A. Fisher: University of Oxford
Deborah Hay: University of Oxford
Mohsin Badat: University of Oxford
Lynn Quek: University of Oxford
Kevin Clark: University of Oxford
Philip Hublitz: University of Oxford
Damien Downes: University of Oxford
Jon Kerry: University of Oxford
Matthew Gosden: University of Oxford
Jelena Telenius: University of Oxford
Jackie A. Sloane-Stanley: University of Oxford
Paula Faustino: National Institute of Health Dr. Ricardo Jorge, Av. Padre Cruz
Andreia Coelho: National Institute of Health Dr. Ricardo Jorge, Av. Padre Cruz
Jessica Doondeea: University of Oxford
Batchimeg Usukhbayar: University of Oxford
Paul Sopp: University of Oxford
Jacqueline A. Sharpe: University of Oxford
Jim R. Hughes: University of Oxford
Paresh Vyas: University of Oxford
Richard J. Gibbons: University of Oxford
Douglas R. Higgs: University of Oxford

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00479-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00479-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00479-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().