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dc.contributor.authorReint, Ganna
dc.contributor.authorLi, Zhuokun
dc.contributor.authorLabun, Kornel
dc.contributor.authorKeskitalo, Salla
dc.contributor.authorSoppa, Inkeri
dc.contributor.authorMamia, Katariina
dc.contributor.authorTolo, Eero
dc.contributor.authorSzymanska, Monika
dc.contributor.authorMeza-Zepeda, Leonardo A
dc.contributor.authorLorenz, Susanne
dc.contributor.authorCieslar-Pobuda, Artur
dc.contributor.authorHu, Xian
dc.contributor.authorBordin, Diana L
dc.contributor.authorStaerk, Judith
dc.contributor.authorValen, Eivind
dc.contributor.authorSchmierer, Bernhard
dc.contributor.authorVarjosalo, Markku
dc.contributor.authorTaipale, Jussi
dc.contributor.authorHaapaniemi, Emma
dc.date.accessioned2022-01-28T14:37:58Z
dc.date.available2022-01-28T14:37:58Z
dc.date.issued2021-12-13
dc.date.submitted2021-11-13
dc.identifier.other75415
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332989
dc.descriptionFunder: Barncancerfonden; FundRef: http://dx.doi.org/10.13039/501100006313
dc.descriptionFunder: Norwegian Research Council; FundRef: http://dx.doi.org/10.13039/501100005416
dc.descriptionFunder: Knut och Alice Wallenbergs Stiftelse; FundRef: http://dx.doi.org/10.13039/501100004063
dc.descriptionFunder: Cancerfonden; FundRef: http://dx.doi.org/10.13039/501100002794
dc.descriptionFunder: Instrumentariumin Tiedesäätiö; FundRef: http://dx.doi.org/10.13039/501100008413
dc.descriptionFunder: Science for Life Laboratory; FundRef: http://dx.doi.org/10.13039/501100009252
dc.descriptionFunder: Academy of Finland; FundRef: http://dx.doi.org/10.13039/501100002341
dc.description.abstractPrecision CRISPR gene editing relies on the cellular homology-directed DNA repair (HDR) to introduce custom DNA sequences to target sites. The HDR editing efficiency varies between cell types and genomic sites, and the sources of this variation are incompletely understood. Here, we have studied the effect of 450 DNA repair protein-Cas9 fusions on CRISPR genome editing outcomes. We find the majority of fusions to improve precision genome editing only modestly in a locus- and cell-type specific manner. We identify Cas9-POLD3 fusion that enhances editing by speeding up the initiation of DNA repair. We conclude that while DNA repair protein fusions to Cas9 can improve HDR CRISPR editing, most need to be optimized to the cell type and genomic site, highlighting the diversity of factors contributing to locus-specific genome editing outcomes.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.subjectResearch Article
dc.subjectCell Biology
dc.subjectCRISPR-Cas9
dc.subjectgene editing
dc.subjectmolecular biology
dc.subjectOther
dc.titleRapid genome editing by CRISPR-Cas9-POLD3 fusion
dc.typeArticle
dc.date.updated2022-01-28T14:37:56Z
prism.publicationNameeLife
prism.volume10
dc.identifier.doi10.17863/CAM.80413
dcterms.dateAccepted2021-11-15
rioxxterms.versionofrecord10.7554/elife.75415
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Tyler, Jessica K
datacite.contributor.supervisorsenior_editor: Tyler, Jessica K
dc.contributor.orcidReint, Ganna [0000-0003-4823-5485]
dc.contributor.orcidLi, Zhuokun [0000-0001-7297-6916]
dc.contributor.orcidSzymanska, Monika [0000-0003-0957-9568]
dc.contributor.orcidHu, Xian [0000-0002-3381-7514]
dc.contributor.orcidStaerk, Judith [0000-0001-8698-6998]
dc.contributor.orcidSchmierer, Bernhard [0000-0002-9082-7022]
dc.contributor.orcidVarjosalo, Markku [0000-0002-1340-9732]
dc.contributor.orcidTaipale, Jussi [0000-0003-4204-0951]
dc.contributor.orcidHaapaniemi, Emma [0000-0002-6693-8208]
dc.identifier.eissn2050-084X
pubs.funder-project-idMinistry of Health and Care Services (279922)


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