{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:35:18Z","timestamp":1791513318461,"version":"4.3.4"},"posted":{"date-parts":[[2026,6,1]]},"group-title":"Genetics","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"IOCB Tech Foundation, Prague, CZ"},{"name":"New York Stem Cell Foundation, New York, US"},{"name":"Korean Fund for Regenerative Medicine, Seoul, KR"},{"name":"Genomic Prediction, New Brunswick, US"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Cas9-based tools enable the introduction of genetic lesions to investigate DNA repair outcomes and edit the genome at disease-relevant loci. DNA double-strand breaks (DSBs) induced by CRISPR\/Cas9 result in frequent aneuploidy and large deletions, revealing a repair deficiency in early human embryos and limiting the clinical application of this technology. Here we evaluated the DNA repair outcomes of DNA nicks and mismatches introduced using base editors in human embryos at two targets,\n                  <jats:italic>PCSK9<\/jats:italic>\n                  and\n                  <jats:italic>HBG<\/jats:italic>\n                  . Editing was efficient and, unlike Cas9-induced DSBs, did not result in either chromosomal abnormalities or large deletions. Small insertions or deletions after base editing were rare, and off-target activity was dependent on the guide RNA. Delivering the base editor as a protein at fertilization or at the pronuclear stage allowed normal development to the blastocyst stage and the derivation of edited stem cell lines. In stark contrast, introduction of the editor as RNA resulted in early embryo arrest. Our results demonstrated that, unlike DSBs, DNA nicks and mismatches are efficiently repaired in human embryos, allowing specific on-target changes without genotoxic consequences.\n                <\/jats:p>","DOI":"10.64898\/2026.05.30.728989","type":"posted-content","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:35:12Z","timestamp":1780378512000},"source":"Crossref","is-referenced-by-count":11,"title":["Efficient base editing and development in human embryos without chromosomal alterations"],"prefix":"10.64898","author":[{"given":"Stepan","family":"Jerabek","sequence":"first","affiliation":[{"name":"Columbia University, Department of Pediatrics, Division of Molecular Genetics, New York, USA"},{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Kim","sequence":"additional","affiliation":[{"name":"Columbia University, Department of Pediatrics, Division of Molecular Genetics, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Sung","sequence":"additional","affiliation":[{"name":"Columbia University, Department of Pediatrics, Division of Molecular Genetics, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanju","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Iuri Roos","family":"Kulmann","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic"},{"name":"Department of Cell Biology, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melisa","family":"Isado","sequence":"additional","affiliation":[{"name":"Columbia University, Department of Pediatrics, Division of Molecular Genetics, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Su","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Korea University, Seoul, Republic of Korea"},{"name":"Center for Biomolecular and Cellular Structure, Institute for Basic Science (IBS), Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Columbia University, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakshi","family":"Bhatele","sequence":"additional","affiliation":[{"name":"Columbia University, Department of Pediatrics, Division of Molecular Genetics, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Kappy","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Columbia University, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangyi","family":"Xu","sequence":"additional","affiliation":[{"name":"Columbia University, Department of Pediatrics, Division of Molecular Genetics, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gue-Ho","family":"Hwang","sequence":"additional","affiliation":[{"name":"Medical Research Center of Genomic Medicine Institute, Seoul National University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Xu","sequence":"additional","affiliation":[{"name":"Genomic Prediction Inc., 675 US Highway One, Suite 126 North Brunswick, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Marin","sequence":"additional","affiliation":[{"name":"Genomic Prediction Inc., 675 US Highway One, Suite 126 North Brunswick, New Jersey, USA"},{"name":"Department of Human Genetics, Rutgers University, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Sun","family":"Woo","sequence":"additional","affiliation":[{"name":"Center for Biomolecular and Cellular Structure, Institute for Basic Science (IBS), Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3615-8566","authenticated-orcid":false,"given":"Sangsu","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea"},{"name":"Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea"},{"name":"Medical Research Center of Genomic Medicine Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Treff","sequence":"additional","affiliation":[{"name":"Genomic Prediction Inc., 675 US Highway One, Suite 126 North Brunswick, New Jersey, USA"},{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers University, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0812-6412","authenticated-orcid":false,"given":"Dieter","family":"Egli","sequence":"additional","affiliation":[{"name":"Columbia University, Department of Pediatrics, Division of Molecular Genetics, New York, USA"},{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Columbia University, New York, USA"},{"name":"Columbia Stem Cell Initiative, Columbia 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