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| Home > Articles > Published articles > TALEN mediated gene editing in a mouse model of Fanconi anemia |
(Centro Nacional de Investigaciones Oncológicas. Grupo de Citogenética Molecular) (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (University of Freiburg. Center for Chronic Immunodeficiency - Medical Center) (Centro de Investigación Biomédica en Red de Enfermedades Raras)| Date: | 2020 |
| Abstract: | The promising ability to genetically modify hematopoietic stem and progenitor cells by precise gene editing remains challenging due to their sensitivity to in vitro manipulations and poor efficiencies of homologous recombination. This study represents the first evidence of implementing a gene editing strategy in a murine safe harbor locus site that phenotypically corrects primary cells from a mouse model of Fanconi anemia A. By means of the co-delivery of transcription activator-like effector nucleases and a donor therapeutic FANCA template to the Mbs85 locus, we achieved efficient gene targeting (23%) in mFA-A fibroblasts. This resulted in the phenotypic correction of these cells, as revealed by the reduced sensitivity of these cells to mitomycin C. Moreover, robust evidence of targeted integration was observed in murine wild type and FA-A hematopoietic progenitor cells, reaching mean targeted integration values of 21% and 16% respectively, that were associated with the phenotypic correction of these cells. Overall, our results demonstrate the feasibility of implementing a therapeutic targeted integration strategy into the m Mbs85 locus, ortholog to the well-validated hAAVS1, constituting the first study of gene editing in mHSC with TALEN, that sets the basis for the use of a new safe harbor locus in mice. |
| Grants: | European Commission 305421 Ministerio de Sanidad, Servicios Sociales e Igualdad EC11/060 Ministerio de Sanidad, Servicios Sociales e Igualdad EC11/550 Ministerio de Economía y Competitividad SAF2015-68073-R Instituto de Salud Carlos III RD12/0019/0023 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Targeted gene repair ; DNA recombination |
| Published in: | Scientific reports, Vol. 10 (April 2020) , art. 6997, ISSN 2045-2322 |
