Unexpected mutations were expected and unrelated to CRISPR-Cas9 activity

Transgenic Res. 2018 Aug;27(4):315-319. doi: 10.1007/s11248-018-0081-2. Epub 2018 May 31.


The scientific journal Nature Methods have just retracted a publication that reported numerous unexpected mutations after a CRISPR-Cas9 experiment based on collecting whole genome sequencing information from one control and two experimental genome edited mice. In the intervening 10 months since publication the data presented have been strongly contested and criticized by the scientific and biotech communities, through publications, open science channels and social networks. The criticism focused on the animal used as control, which was derived from the same mouse strain as the experimental individuals but from an unrelated sub-colony, hence control and experimental mice were genetically divergent. The most plausible explanation for the vast majority of the reported unexpected mutations were the expected underlying genetic polymorphisms that normally accumulate in two different colonies of the same mouse strain which occur as a result of spontaneous mutations and genetic drift. Therefore, the reported mutations were most likely not related to CRISPR-Cas9 activity.

Keywords: CRISPR; Cas9; Gene therapy; Genome editing applications; Off target mutations; Safety.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CRISPR-Cas Systems / genetics*
  • Mice
  • Mutagenesis
  • Mutation / genetics*
  • Polymorphism, Genetic*