The 2017 Nature Methods paper from researchers at Stanford University, Columbia University and University of Iowa claimed CRISPR gene editing led to an unexpected high level of off-target mutations. In the retraction, the journal said there were insufficient data to support the claim and cited the need for a control comparison between parent and offspring mice to determine whether natural genetic variation clouded the authors' interpretation of CRISPR-mediated off-target mutations (see BioCentury Extra, May 30, 2017).
The journal said two of the six study authors agreed with the retraction, and four did not. It did not provide the authors’ reasoning.
The findings of the group's expanded bioRxiv study, which used two mouse strains with different genetic backgrounds, suggested CRISPR editing may not introduce numerous and unintended mutations (see BioCentury Extra, March 26).
Others, including executives at Editas Medicine Inc. (NASDAQ:EDIT) and Editas advisor George Church, have published studies showing that natural genetic variations prior to CRISPR treatment were likely the cause of observed variants (see BioCentury Extra, June 22, 2017).
Based on public responses to the original Nature Methods study, the journal published an editorial note in June stating the conclusions of the paper "are subject to criticisms that are being considered by editors," and issued an editorial expression of concern in July (see BioCentury Extra, June 16, 2017).
Stanford professor Vinit Mahajan, a corresponding author on the Nature Methods paper, told BioCentury his group is using whole genome sequencing on additional CRISPR treated mice to elucidate CRISPR's off-target effects.