2026-04-26T23:12:00Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/261462025-12-18T12:51:55Zcom_20.500.12105_2273com_20.500.12105_2202col_20.500.12105_19571

00925njm 22002777a 4500 dc Román-Rodríguez, Francisco José author Ugalde, Laura author Álvarez, Lara author Díez, Begoña author Ramírez, María José author Risueño, Cristina author Cortón, Marta author Bogliolo, Massimo author Bernal, Sara author March, Francesca author Ayuso, Carmen author Hanenberg, Helmut author Sevilla, Julián author Rodriguez Perales, Sandra author Torres-Ruiz, Raul author Surrallés, Jordi author Bueren, Juan Antonio author Río, Paula author 2019-11-07 Non-homologous end-joining (NHEJ) is the preferred mechanism used by hematopoietic stem cells (HSCs) to repair double-stranded DNA breaks and is particularly increased in cells deficient in the Fanconi anemia (FA) pathway. Here, we show feasible correction of compromised functional phenotypes in hematopoietic cells from multiple FA complementation groups, including FA-A, FA-C, FA-D1, and FA-D2. NHEJ-mediated repair of targeted CRISPR-Cas9-induced DNA breaks generated compensatory insertions and deletions that restore the coding frame of the mutated gene. NHEJ-mediated editing efficacy was initially verified in FA lymphoblastic cell lines and then in primary FA patient-derived CD34 cells, which showed marked proliferative advantage and phenotypic correction both in vitro and after transplantation. Importantly, and in contrast to homologous directed repair, NHEJ efficiently targeted primitive human HSCs, indicating that NHEJ editing approaches may constitute a sound alternative for editing self-renewing human HSCs and consequently for treatment of FA and other monogenic diseases affecting the hematopoietic system. Cell Stem Cell . 2019 Nov 7;25(5):607-621 https://hdl.handle.net/20.500.12105/26146 31543367 Cell Stem Cell CRISPR/Cas9 system Fanconi anemia gene editing hematopoietic stem and progenitor cells indels non-homologous end-joining NHEJ-Mediated Repair of CRISPR-Cas9-Induced DNA Breaks Efficiently Corrects Mutations in HSPCs from Patients with Fanconi Anemia.