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dc.contributor.authorDiez, Begoña
dc.contributor.authorGenovese, Pietro
dc.contributor.authorRoman-Rodriguez, Francisco J
dc.contributor.authorAlvarez, Lara
dc.contributor.authorSchiroli, Giulia
dc.contributor.authorUgalde, Laura
dc.contributor.authorRodriguez Perales, Sandra 
dc.contributor.authorSevilla, Julian
dc.contributor.authorDiaz de Heredia, Cristina
dc.contributor.authorHolmes, Michael C
dc.contributor.authorLombardo, Angelo
dc.contributor.authorNaldini, Luigi
dc.contributor.authorBueren, Juan Antonio
dc.contributor.authorRio, Paula
dc.date.accessioned2019-02-06T11:07:29Z
dc.date.available2019-02-06T11:07:29Z
dc.date.issued2017
dc.identifier.citationEMBO Mol Med. 2017;9(11):1574-1588.es_ES
dc.identifier.issn1757-4676es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7133
dc.description.abstractGene 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.es_ES
dc.description.sponsorshipThe authors would like to thank Aurora de la Cal for her assistance with thecoordination in the delivery of the samples from the patients. RebecaSánchez-Domínguez for her expertise in flow cytometry and Centro de Trans-fusiones de la Comunidad de Madrid for providing cord blood samples. Theauthors are also indebted to the FA patients, families, and clinicians from theFA spanish network. This work was supported by grants from the“7th Frame-work Program European Commission (HEALTH-F5-2012-305421; EUROFAN-COLEN)”,“Ministerio de Sanidad, Servicios Sociales e Igualdad”(EC11/060andEC11/550),“Ministerio de Economía, Comercio y Competitividad y FondoEuropeo de Desarrollo Regional (FEDER)”(SAF2015-68073-R), and“Fondo deInvestigaciones Sanitarias, Instituto de Salud Carlos III”(RD12/0019/0023). Theauthors also thank the Fundación Marcelino Botín for promoting translationalresearch at the Hematopoietic Innovative Therapies Division of the CIEMAT.CIBERER is an initiative of the Instituto de Salud Carlos III, Spain.es_ES
dc.language.isoenges_ES
dc.publisherWiley es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCD34+ cellses_ES
dc.subjectFanconi anemiaes_ES
dc.subjectGene editinges_ES
dc.subjectHematopoietic stem and progenitor cellses_ES
dc.subjectZinc finger nucleaseses_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntigens, CD34 es_ES
dc.subject.meshBase Sequence es_ES
dc.subject.meshCells, Cultured es_ES
dc.subject.meshDependovirus es_ES
dc.subject.meshFanconi Anemia es_ES
dc.subject.meshFanconi Anemia Complementation Group A Protein es_ES
dc.subject.meshFetal Blood es_ES
dc.subject.meshGene Editing es_ES
dc.subject.meshGenetic Vectors es_ES
dc.subject.meshHematopoietic Stem Cell Transplantation es_ES
dc.subject.meshHematopoietic Stem Cells es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred NOD es_ES
dc.subject.meshMice, SCID es_ES
dc.subject.meshMice, Transgenic es_ES
dc.subject.meshReactive Oxygen Species es_ES
dc.subject.meshZinc Finger Nucleases es_ES
dc.titleTherapeutic gene editing in CD34+ hematopoietic progenitors from Fanconi anemia patientses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID28899930es_ES
dc.format.volume9es_ES
dc.format.number11es_ES
dc.format.page1574-1588es_ES
dc.identifier.doi10.15252/emmm.201707540es_ES
dc.contributor.funderMinisterio de Sanidad y Consumo (España) 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1757-4684es_ES
dc.relation.publisherversionhttps://doi.org/10.15252/emmm.201707540.es_ES
dc.identifier.journalEMBO molecular medicinees_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Citogenética Moleculares_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7HEALTH-FS-2012-305421es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/EC11/060es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/EC11/550es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2015-68073-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0019/0023es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
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