{"entity": "publication", "iuid": "7feac7b384bd4538b6116d30a4f37f9d", "timestamp": "2026-07-12T18:51:58.533Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7feac7b384bd4538b6116d30a4f37f9d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7feac7b384bd4538b6116d30a4f37f9d"}}, "title": "CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations.", "authors": [{"family": "H\u00f6ijer", "given": "Ida", "initials": "I", "orcid": "0000-0002-3915-3384", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba4ce20b1b447ada4fdc8256211436e.json"}}, {"family": "Emmanouilidou", "given": "Anastasia", "initials": "A"}, {"family": "\u00d6stlund", "given": "Rebecka", "initials": "R", "orcid": "0000-0003-4460-7245", "researcher": {"href": "https://publications.scilifelab.se/researcher/03b1d5938f74406ebffb5b49ba5b182c.json"}}, {"family": "van Schendel", "given": "Robin", "initials": "R", "orcid": "0000-0001-7068-0679", "researcher": {"href": "https://publications.scilifelab.se/researcher/6aa5a36e5b534bab8a04b4c8f040abb4.json"}}, {"family": "Bozorgpana", "given": "Selma", "initials": "S"}, {"family": "Tijsterman", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8465-9002", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1e816845f6048e2a2c7dc29e9a13cdf.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U", "orcid": "0000-0002-6316-3355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8739f0f42c44019ab88a49db350a4f2.json"}}, {"family": "den Hoed", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8081-428X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d712cc087d344b15ab9a7971640acebe.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2022-02-02", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "13", "issue": "1", "pages": "627"}, "abstract": "CRISPR-Cas9 genome editing has potential to cure diseases without current treatments, but therapies must be safe. Here we show that CRISPR-Cas9 editing can introduce unintended mutations in vivo, which are passed on to the next generation. By editing fertilized zebrafish eggs using four guide RNAs selected for off-target activity in vitro, followed by long-read sequencing of DNA from >1100 larvae, juvenile and adult fish across two generations, we find that structural variants (SVs), i.e., insertions and deletions \u226550 bp, represent 6% of editing outcomes in founder larvae. These SVs occur both at on-target and off-target sites. Our results also illustrate that adult founder zebrafish are mosaic in their germ cells, and that 26% of their offspring carries an off-target mutation and 9% an SV. Hence, pre-testing for off-target activity and SVs using patient material is advisable in clinical applications, to reduce the risk of unanticipated effects with potentially large implications.", "doi": "10.1038/s41467-022-28244-5", "pmid": "35110541", "labels": {"National Genomics Infrastructure": "Technology development", "NGI Uppsala (Uppsala Genome Center)": "Technology development", "NGI Long read": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8810904"}, {"db": "pii", "key": "10.1038/s41467-022-28244-5"}], "notes": [], "created": "2022-02-17T14:45:40.515Z", "modified": "2024-01-16T13:48:37.595Z"}