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

ABSTRACT: CRISPR-Cas9 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 introduced 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

SUBMITTER: Iyer V 

PROVIDER: S-EPMC6057650 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature