{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Carusillo A"],"funding":["German Research Foundation","European Union's Horizon 2020","University of Freiburg","Medical Informatics Funding Scheme"],"pagination":["4660-4673"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10201422"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["51(9)"],"pubmed_abstract":["Precise genome editing requires the resolution of nuclease-induced DNA double strand breaks (DSBs) via the homology-directed repair (HDR) pathway. In mammals, this is typically outcompeted by non-homologous end-joining (NHEJ) that can generate potentially genotoxic insertion/deletion mutations at DSB sites. Because of higher efficacy, clinical genome editing has been restricted to imperfect but efficient NHEJ-based approaches. Hence, strategies that promote DSB resolution via HDR are essential to facilitate clinical transition of HDR-based editing strategies and increase safety. Here we describe a novel platform that consists of a Cas9 fused to DNA repair factors to synergistically inhibit NHEJ and favor HDR for precise repairing of Cas-induced DSBs. Compared to canonical CRISPR/Cas9, the "],"journal":["Nucleic acids research"],"pubmed_title":["A novel Cas9 fusion protein promotes targeted genome editing with reduced mutational burden in primary human cells."],"pmcid":["PMC10201422"],"funding_grant_id":["765269","3861/3-1","EkoEstMed–FKZ 01ZZ2015"],"pubmed_authors":["Chmielewski KO","Mussolino C","Klermund J","Schafer R","Turk D","Carusillo A","Mosti L","Cornu TI","Rhiel M","Haider S","Andrieux G","Cathomen T"],"additional_accession":[]},"is_claimable":false,"name":"A novel Cas9 fusion protein promotes targeted genome editing with reduced mutational burden in primary human cells.","description":"Precise genome editing requires the resolution of nuclease-induced DNA double strand breaks (DSBs) via the homology-directed repair (HDR) pathway. In mammals, this is typically outcompeted by non-homologous end-joining (NHEJ) that can generate potentially genotoxic insertion/deletion mutations at DSB sites. Because of higher efficacy, clinical genome editing has been restricted to imperfect but efficient NHEJ-based approaches. Hence, strategies that promote DSB resolution via HDR are essential to facilitate clinical transition of HDR-based editing strategies and increase safety. Here we describe a novel platform that consists of a Cas9 fused to DNA repair factors to synergistically inhibit NHEJ and favor HDR for precise repairing of Cas-induced DSBs. Compared to canonical CRISPR/Cas9, the ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2026-05-28T17:51:18.988Z","creation":"2025-04-04T14:30:00.915Z"},"accession":"S-EPMC10201422","cross_references":{"pubmed":["37070192"],"doi":["10.1093/nar/gkad255"]}}