Scientists from the CRISPR-based firms Intellia Therapeutics and Editas Medicine have written open letters to the journal Nature Methods, stating that the conclusions of the study are 'unsubstantiated'.
'Our opinion is that the authors failed to sufficiently control the reported study in such a way that one could conclude that CRISPR induces the observed mutations,' said Editas' letter, co-signed by 13 of the company's scientists. 'In our view, the genetic differences seen in this comparative analysis were likely present prior to editing with CRISPR.'
Dr Nessan Bermingham, CEO of Intellia, has called for the paper to be retracted on grounds of flawed design and interpretation. Both firms' share prices have been negatively impacted by the study, and some companies saw a fall of up to 15 percent.
The study reported the discovery of over 100 large deletions or insertions in the genome of two mice which had previously undergone CRISPR genome editing. These had not been anticipated by other widely used methods to detect the accuracy of the technique, the authors claimed (see BioNews 903).
The study has gathered a lot of attention since its publication last month. A number of scientists have highlighted flaws within the research, including the small number of animals and misidentification of off-targets effects. Many have offered alternative explanations for the findings.
Talking to The Scientist, Dr Gaétan Burgio, a geneticist from the Australian National University, Canberra, points out that the use of published sequence data rather than non-edited control animals kept in the same laboratory conditions may mean that the study was unable to 'tease out which variants are due to the natural genetic variation and which ones are CRISPR-related.'
In response to the criticism, a spokesperson at Springer Nature, which publishes Nature Methods, told MIT Technology Review, 'We are carefully considering all concerns that have been raised with us and are discussing them with the authors.'
Scientists are aware that using CRISPR will sometimes result in unintended genomic changes. 'Getting people to talk about the need for controls is a good outcome of this whole thing. I think the data is perfectly fine. It's just the interpretation of it that to me seems odd,' said Dr Matthew Taliaferro, who studies genome editing at Massachusetts Institute of Technology.
Co-author of the study in question, Dr Vinit Mahajan of Stanford University, told The Scientist he remains 'very excited' about the potential of CRISPR, though admits that they cannot be completely certain that it caused all of the observed mutations. However, 'if you make an observation that's important enough to share with your community, you're obligated to do that right away,' he told WIRED.