Last May, a journal published findings suggesting that CRISPR's revolutionary gene-editing technique could actually be quite dangerous. The paper caused a bit of a turmoil in the biotech world, which sees CRISPR as an important tool in the fight against disease. But it did not take long for the study to raise serious skepticism. This week, the journal that published the publication Nature Methods finally withdrew it.
In the study, researchers found that when they used CRISPR to cure blindness by altering the DNA in mice, it resulted in more than a thousand unintended effects on other genes. That was a really big deal. It has long been known that even if a gene editor like CRISPR is so accurate, off-target effects can be a nuisance potential side effect. But more than a thousand such unintentional edits are a lot. This, according to the authors, means that CRISPR requires significant fine-tuning before it could be the miraculous cure for as many human diseases as the world hoped for. Biotech shares crashed. The scientific community broke out.
Soon, however, other researchers accused the authors of the study of "reckless errors" and errors in the methodology of their mouse study. In February, the work continued to be discredited when scientists at the Wellcome Sanger Institute in the UK re-enacted the original study and found that there were no significant unexpected mutations. But the last nail in the CRISPR coffin seems to have come this week, as the original authors of the study published a new pre-print paper in which they sought and did not use their earlier mouse-over methodology for possible off-target effects in a new mouse experiment find an excess of unintentional genetic mutations, as they had in their initial work.
"Our previous publication suggested that CRISPR-Cas9 editing at the zygotic stage unexpectedly introduces a multitude of subtle but unintentional mutations, an interpretation that does not cause a surprising number of questions," they wrote.
"These results from the entire genome sequencing level support the idea that CRISPR-Cas9 editing may, in certain cases, precisely process the genome at the organismic level and not many, unintended, mutations outside the target."
Few Days later ̵
"There was not enough data to substantiate the claim of unexpected off-target effects due to CRISPR in an article published in Nature Methods, and more work is needed to determine if such events occur in vivo." , wrote the magazine in an editorial that explained the decision.
The exact genetic makeup of the parent mice of the laboratory mice was not known, and the control group of the mice and the CRISPRD mice were not siblings, the editorial explained, so it was impossible for the researchers to tell if the genetic Differences between the control mice and the CRISPR® d mice were due to off-target effects or only natural variation.
"The central claim of the paper is therefore not adequately supported by the data, which is the reason why the paper was withdrawn," the editorial said.
"The original work has been reviewed by experts, but we should have looked for at least one additional arbitrator with expertise in the genetics of inbred mouse strains."
The magazine also published five of these reviews of the original work in its latest issue.
But, as the editorial points out, little is known about the off-target effects of CRISPR when used in the body of a human or animal. And off-target effects are still a real problem.
"The question of whether CRISPR can be safely used in vivo is high for many," reads the editorial. "But for no one are they higher than for the people in whom this technology can be used in the future, and they owe a careful and rigorous response."