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Rapid genome editing by CRISPR-Cas9-POLD3 fusion

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Labun, Kornel 
Keskitalo, Salla 
Soppa, Inkeri 


Precision 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.


Funder: Barncancerfonden; FundRef:

Funder: Norwegian Research Council; FundRef:

Funder: Knut och Alice Wallenbergs Stiftelse; FundRef:

Funder: Cancerfonden; FundRef:

Funder: Instrumentariumin Tiedesäätiö; FundRef:

Funder: Science for Life Laboratory; FundRef:

Funder: Academy of Finland; FundRef:


Research Article, Cell Biology, CRISPR-Cas9, gene editing, molecular biology, Other

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eLife Sciences Publications, Ltd
Ministry of Health and Care Services (279922)