Authors of the article stating that CRISPR gene-editing technology causes thousands of unexpected off-target effects reported that study results may have been wrong.
One year after the publication, sensational article “Unexpected mutations after CRISPR-Cas9 editing in vivo” was retracted from Nature Methods journal.
Results of the study, published in May 2017, gave rise to great scandal. A deluge of criticism was brought on both by international scientific community and by major biotechnological companies. In particular, Editorial Office of Nature Methods was deluged with seething letters sent by the representatives of Intellia Therapeutics and Editas Medicine, since the value of their securities dropped dramatically upon the publication of this article. The criticism was mainly caused by the methodology of the study.
CRISPR/Cas9 system is a sort of virus-induced immunity for bacteria, that detects virus genes located in the DNA and eliminates them in a targeted way. This very system allows for quick editing of genome sections of any cell. However, experiments conducted upon the discovery of CRISPR/Cas9 have shown that genome editing may also have off-target effects – cutting the wrong section of DNA, for instance, which causes unexpected mutations.
Preliminary estimations of the specialists showed that there were few of such unexpected changes, however the team of researchers at Stanford and Columbia Universities (the USA) made in-depth study of this phenomenon. This is how controversial article “Unexpected mutations after CRISPR-Cas9 editing in vivo” came into existence.
To have a more precise idea of the consequences caused by genome editing, mistrustful researchers examined two lab mice, who previously had their blindness-causing mutation cured using CRISPR/Cas9 system. DNA of another “unedited” mouse was treated as a “control group”.
Whole genome analysis that considered all mutations common to the two independently generated CRISPR edited mice was 1,397 single nucleotide variants and 117 indels.
“We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome,” – said co-author of the article Stephen Tsang.
Is CRISPR really so dangerous
Publication of this article touched off true panic among scientific community. One of its consequences was imposition of limitations on experiments involving genome editing system.
The representatives of the global scientific community and experts from biotechnological companies blamed authors of the study for their failure to sequence the genome of parents of that very “edited” mice. According to them, this additional study could determine actual impact of CRISPR/Cas9 on revealed genetic variations.
Moreover, numerous critics declared that some of the mutations detected by researchers at Stanford and Columbia Universities simply could not have been a consequence of genome editing, since such type of modifications are outside the radius of CRISPR’s capacity.
Researches were also reproached for ridiculous number of laboratory animals – it was clearly insufficient to make such radical and tangible conclusions.
George Church, Professor of Genetics at Harvard University, Co-founder at Wyss Institute for Biologically Inspired Engineering, Project Manager at Personal Genome Project, stated explicitly that article should be retracted or, at the very least, supplemented by comments about important uncovered problems.
Thorough internal inspection conducted by Nature Methods drew to conclusion about insufficient data to support the claim of unexpected off-target effects due to CRISPR. Moreover, the team of researchers, whose article sparked panic among scientific community, failed to to achieve the same results. And finally, almost a whole year following the publication of article, it was retracted.
Only two of the six authors of the retracted article have concurred with the decision. In their new article the team of researchers admitted that findings from their 2017 year’s research were erroneous, and reported that despite the retraction of article, they will keep on working in this direction.