Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-05

AUTHORS

Van Trung Chu, Timm Weber, Benedikt Wefers, Wolfgang Wurst, Sandrine Sander, Klaus Rajewsky, Ralf Kühn

ABSTRACT

The insertion of precise genetic modifications by genome editing tools such as CRISPR-Cas9 is limited by the relatively low efficiency of homology-directed repair (HDR) compared with the higher efficiency of the nonhomologous end-joining (NHEJ) pathway. To enhance HDR, enabling the insertion of precise genetic modifications, we suppressed the NHEJ key molecules KU70, KU80 or DNA ligase IV by gene silencing, the ligase IV inhibitor SCR7 or the coexpression of adenovirus 4 E1B55K and E4orf6 proteins in a 'traffic light' and other reporter systems. Suppression of KU70 and DNA ligase IV promotes the efficiency of HDR 4-5-fold. When co-expressed with the Cas9 system, E1B55K and E4orf6 improved the efficiency of HDR up to eightfold and essentially abolished NHEJ activity in both human and mouse cell lines. Our findings provide useful tools to improve the frequency of precise gene modifications in mammalian cells. More... »

PAGES

543

Journal

TITLE

Nature Biotechnology

ISSUE

5

VOLUME

33

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt.3198

DOI

http://dx.doi.org/10.1038/nbt.3198

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008895789

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25803306


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