Off- and on-target effects of genome editing in mouse embryos

J Reprod Dev. 2019 Feb 8;65(1):1-5. doi: 10.1262/jrd.2018-128. Epub 2018 Dec 6.

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-based genome editing technology has enabled manipulation of the embryonic genome. Unbiased whole genome sequencing comparing parents to progeny has revealed that the rate of Cas9-induced mutagenesis in mouse embryos is indistinguishable from the background rate of de novo mutation. However, establishing the best practice to confirm on-target alleles of interest remains a challenge. We believe that improvement in editing strategies and screening methods for founder mice will contribute to the generation of quality-controlled animals, thereby ensuring reproducibility of results in animal studies and advancing the 3Rs (replacement, reduction, and refinement).

Keywords: CRISPR; Cas9; Genome editing; Genotyping; Off-target effect.

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • CRISPR-Associated Protein 9 / genetics*
  • CRISPR-Cas Systems / genetics*
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics
  • Embryo, Mammalian*
  • Gene Editing / methods*
  • Mice
  • Mice, Inbred C57BL
  • Mutagenesis*
  • Reproducibility of Results
  • Whole Genome Sequencing

Substances

  • CRISPR-Associated Protein 9