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

Detalhes bibliográficos
Autor(a) principal: Mettananda, Sachith
Data de Publicação: 2017
Outros Autores: Fisher, Chris A., Hay, Deborah, Badat, Mohsin, Quek, Lynn, Clark, Kevin, Hublitz, Philip, Downes, Damien, Kerry, Jon, Gosden, Matthew, Telenius, Jelena, Sloane-Stanley, Jackie A., Faustino, Paula, Coelho, Andreia, Doondeea, Jessica, Usukhbayar, Batchimeg, Sopp, Paul, Sharpe, Jacqueline A., Hughes, Jim R., Vyas, Paresh, Gibbons, Richard J., Higgs, Douglas R.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/47091
Resumo: © The Author(s) 2017. Open Access. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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spelling Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia© The Author(s) 2017. Open Access. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.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.This work was supported by grants to D.R.H. by the UK Medical Research Council (grant number MC_UU_12025/ unit programme MC_UU_12009/4) and the NIHR Oxford Biomedical Research Center. S.M. is a Commonwealth Scholar, funded by the UK government.Springer NatureRepositório da Universidade de LisboaMettananda, SachithFisher, Chris A.Hay, DeborahBadat, MohsinQuek, LynnClark, KevinHublitz, PhilipDownes, DamienKerry, JonGosden, MatthewTelenius, JelenaSloane-Stanley, Jackie A.Faustino, PaulaCoelho, AndreiaDoondeea, JessicaUsukhbayar, BatchimegSopp, PaulSharpe, Jacqueline A.Hughes, Jim R.Vyas, PareshGibbons, Richard J.Higgs, Douglas R.2021-03-26T12:23:49Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/47091engNat Commun. 2017 Sep 4;8(1):42410.1038/s41467-017-00479-72041-1723info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:49:44Zoai:repositorio.ul.pt:10451/47091Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:59:10.154584Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia
title Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia
spellingShingle Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia
Mettananda, Sachith
title_short Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia
title_full Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia
title_fullStr Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia
title_full_unstemmed Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia
title_sort Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia
author Mettananda, Sachith
author_facet Mettananda, Sachith
Fisher, Chris A.
Hay, Deborah
Badat, Mohsin
Quek, Lynn
Clark, Kevin
Hublitz, Philip
Downes, Damien
Kerry, Jon
Gosden, Matthew
Telenius, Jelena
Sloane-Stanley, Jackie A.
Faustino, Paula
Coelho, Andreia
Doondeea, Jessica
Usukhbayar, Batchimeg
Sopp, Paul
Sharpe, Jacqueline A.
Hughes, Jim R.
Vyas, Paresh
Gibbons, Richard J.
Higgs, Douglas R.
author_role author
author2 Fisher, Chris A.
Hay, Deborah
Badat, Mohsin
Quek, Lynn
Clark, Kevin
Hublitz, Philip
Downes, Damien
Kerry, Jon
Gosden, Matthew
Telenius, Jelena
Sloane-Stanley, Jackie A.
Faustino, Paula
Coelho, Andreia
Doondeea, Jessica
Usukhbayar, Batchimeg
Sopp, Paul
Sharpe, Jacqueline A.
Hughes, Jim R.
Vyas, Paresh
Gibbons, Richard J.
Higgs, Douglas R.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Mettananda, Sachith
Fisher, Chris A.
Hay, Deborah
Badat, Mohsin
Quek, Lynn
Clark, Kevin
Hublitz, Philip
Downes, Damien
Kerry, Jon
Gosden, Matthew
Telenius, Jelena
Sloane-Stanley, Jackie A.
Faustino, Paula
Coelho, Andreia
Doondeea, Jessica
Usukhbayar, Batchimeg
Sopp, Paul
Sharpe, Jacqueline A.
Hughes, Jim R.
Vyas, Paresh
Gibbons, Richard J.
Higgs, Douglas R.
description © The Author(s) 2017. Open Access. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01T00:00:00Z
2021-03-26T12:23:49Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/47091
url http://hdl.handle.net/10451/47091
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Nat Commun. 2017 Sep 4;8(1):424
10.1038/s41467-017-00479-7
2041-1723
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dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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