2026-08-05T11:42:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/71332024-11-29T19:21:11Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Diez, Begoña
author
Genovese, Pietro
author
Roman-Rodriguez, Francisco J
author
Alvarez, Lara
author
Schiroli, Giulia
author
Ugalde, Laura
author
Rodriguez Perales, Sandra
author
Sevilla, Julian
author
Diaz de Heredia, Cristina
author
Holmes, Michael C
author
Lombardo, Angelo
author
Naldini, Luigi
author
Bueren, Juan Antonio
author
Rio, Paula
funder
Ministerio de Sanidad y Consumo (España)
funder
Ministerio de Economía y Competitividad (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2019-02-06T11:07:29Z
2019-02-06T11:07:29Z
2017
EMBO Mol Med. 2017;9(11):1574-1588.
10.15252/emmm.201707540
1757-4684
1757-4676
EMBO molecular medicine
28899930
http://hdl.handle.net/20.500.12105/7133
Gene targeting constitutes a new step in the development of gene therapy for inherited diseases. Although previous studies have shown the feasibility of editing fibroblasts from Fanconi anemia (FA) patients, here we aimed at conducting therapeutic gene editing in clinically relevant cells, such as hematopoietic stem cells (HSCs). In our first experiments, we showed that zinc finger nuclease (ZFN)-mediated insertion of a non-therapeutic EGFP-reporter donor in the AAVS1 "safe harbor" locus of FA-A lymphoblastic cell lines (LCLs), indicating that FANCA is not essential for the editing of human cells. When the same approach was conducted with therapeutic FANCA donors, an efficient phenotypic correction of FA-A LCLs was obtained. Using primary cord blood CD34+ cells from healthy donors, gene targeting was confirmed not only in in vitro cultured cells, but also in hematopoietic precursors responsible for the repopulation of primary and secondary immunodeficient mice. Moreover, when similar experiments were conducted with mobilized peripheral blood CD34+ cells from FA-A patients, we could demonstrate for the first time that gene targeting in primary hematopoietic precursors from FA patients is feasible and compatible with the phenotypic correction of these clinically relevant cells.
eng
CD34+ cells
Fanconi anemia
Gene editing
Hematopoietic stem and progenitor cells
Zinc finger nucleases
Therapeutic gene editing in CD34+ hematopoietic progenitors from Fanconi anemia patients
journal article
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TherapeuticgeneeditinginCD34+_2017.pdf
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TherapeuticgeneeditinginCD34+_2017.pdf.txt