Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,915 bioRxiv papers from 266,490 authors.

No unexpected CRISPR-Cas9 off-target activity revealed by trio sequencing of gene-edited mice

By Vivek Iyer, Katharina Boroviak, Mark Thomas, Brendan Doe, Edward Ryder, David Adams

Posted 09 Feb 2018
bioRxiv DOI: 10.1101/263129 (published DOI: 10.1371/journal.pgen.1007503)

CRISPR-Cas technologies have transformed genome-editing of experimental organisms and have immense therapeutic potential. Despite significant advances in our understanding of the CRISPR-Cas9 system, concerns remain over the potential for off-target effects. Recent studies have addressed these concerns using whole-genome sequencing (WGS) of gene-edited embryos or animals to search for de novo mutations (DNMs), which may represent candidate changes induced by poor editing fidelity. Critically, these studies used strain-matched but not pedigree-matched controls and thus were unable to reliably distinguish generational or colony-related differences from true DNMs. Here we used a trio design and whole genome sequenced 8 parents and 19 embryos, where 10 of the embryos were mutagenised with well-characterised gRNAs targeting the coat colour Tyrosinase (Tyr) locus. Detailed analyses of these whole genome data allowed us to conclude that if CRISPR mutagenesis were causing SNV or indel off-target mutations in treated embryos, then the number of these mutations is not statistically distinguishable from the background rate of DNMs occurring due to other processes.

Download data

  • Downloaded 2,452 times
  • Download rankings, all-time:
    • Site-wide: 1,442 out of 57,915
    • In bioengineering: 19 out of 1,118
  • Year to date:
    • Site-wide: 11,703 out of 57,915
  • Since beginning of last month:
    • Site-wide: 27,164 out of 57,915

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News