Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci.

ABSTRACT: The CRISPR-Cas9 nuclease system holds enormous potential for therapeutic genome editing of a wide spectrum of diseases. Large efforts have been made to further understanding of on- and off-target activity to assist the design of CRISPR-based therapies with optimized efficacy and safety. However, current efforts have largely focused on the reference genome or the genome of cell lines to evaluate guide RNA (gRNA) efficiency, safety, and toxicity. Here, we examine the effect of human genetic variation on both on- and off-target specificity. Specifically, we utilize 7,444 whole-genome sequences to examine the effect of variants on the targeting specificity of ∼3,000 gRNAs across 30 therapeutically implicated loci. We demonstrate that human genetic variation can alter the off-target landscape g

SUBMITTER: Lessard S 

PROVIDER: S-EPMC5748207 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature