{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:02:12Z","timestamp":1791576132073,"version":"4.3.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Union's Horizon 2020","award":["765269"],"award-info":[{"award-number":["765269"]}]},{"DOI":"10.13039\/501100003122","name":"German Research Foundation","doi-asserted-by":"publisher","award":["3861\/3-1"],"award-info":[{"award-number":["3861\/3-1"]}],"id":[{"id":"10.13039\/501100003122","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Informatics Funding Scheme","award":["EkoEstMed\u2013FKZ 01ZZ2015"],"award-info":[{"award-number":["EkoEstMed\u2013FKZ 01ZZ2015"]}]},{"DOI":"10.13039\/501100002714","name":"University of Freiburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002714","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 increase in error-free editing ranges from 1.5-fold to 7-fold in multiple cell lines and in primary human cells. This novel CRISPR\/Cas9 platform accepts clinically relevant repair templates, such as oligodeoxynucleotides (ODNs) and adeno-associated virus (AAV)-based vectors, and has a lower propensity to induce chromosomal translocations as compared to benchmark CRISPR\/Cas9. The observed reduced mutational burden, resulting from diminished indel formation at on- and off-target sites, provides a remarkable gain in safety and advocates this novel CRISPR system as an attractive tool for therapeutic applications depending on precision genome editing.<\/jats:p>","DOI":"10.1093\/nar\/gkad255","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T02:23:41Z","timestamp":1681784621000},"page":"4660-4673","source":"Crossref","is-referenced-by-count":35,"title":["A novel Cas9 fusion protein promotes targeted genome editing with reduced mutational burden in primary human cells"],"prefix":"10.1093","volume":"51","author":[{"given":"Antonio","family":"Carusillo","sequence":"first","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Ph.D. Program, Faculty of Biology, University of Freiburg , Freiburg \u00a079106, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibtain","family":"Haider","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Ph.D. Program, Faculty of Biology, University of Freiburg , Freiburg \u00a079106, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Rhiel","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"T\u00fcrk","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay\u00a0O","family":"Chmielewski","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Ph.D. Program, Faculty of Biology, University of Freiburg , Freiburg \u00a079106, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Klermund","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mosti","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffroy","family":"Andrieux","sequence":"additional","affiliation":[{"name":"Institute of Medical Bioinformatics and Systems Medicine, Medical Center \u2013 University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Faculty of Medicine, University of Freiburg , 79106 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-W\u00fcrttemberg-Hessen gGmbH, Goethe University Hospital , Frankfurt am Main, 60596 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana\u00a0I","family":"Cornu","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Faculty of Medicine, University of Freiburg , 79106 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Cathomen","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Faculty of Medicine, University of Freiburg , 79106 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2073-1110","authenticated-orcid":false,"given":"Claudio","family":"Mussolino","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg , Freiburg \u00a079106, Germany"},{"name":"Faculty of Medicine, University of Freiburg , 79106 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,18]]},"reference":[{"key":"2023052209000149700_B1","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.3390\/cells9071665","article-title":"DNA damage: from threat to treatment","volume":"9","author":"Carusillo","year":"2020","journal-title":"Cells"},{"key":"2023052209000149700_B2","first-page":"1559","article-title":"Genome editing: a perspective on the application of CRISPR\/Cas9 to study human diseases (review)","volume":"43","author":"Rodriguez-Rodriguez","year":"2019","journal-title":"Int. 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