Crispr-Cas9 would cause involuntary and potentially deleterious mutations

The Crispr-Cas9 experimental technique, used to modify faulty genes and on which medicine has high hopes, is less precise than was thought and causes unexpected mutations, according to a study published Monday, July 16, 2018. These genetic scissors caused frequent " " and "" mutations in experiments conducted on mice and human cells as part of the study, published in the journal Nature Biotechnology .

CRISPR-CAS9 . Crispr-Cas9 is a major discovery unveiled in 2012, attributed to a Franco-American women's duo, Emmanuelle Charpentier and Jennifer Doudna, and frequently cited for the awarding of the Nobel Prize. It is a bacterial protein that serves as a rudimentary immune system. It has the main characteristic of being able to recognize and cut a particular DNA sequence. Modified by researchers to recognize the sequence of their choice, Crispr-Cas9 can potentially correct mutations and become the pivot of gene therapies to treat many genetic diseases.

Mutations hitherto undetected because they are too far removed from the modified site

Previous work has concluded that unexpected mutations in the DNA portion published by Crispr-Cas9 remain rare, explain the authors of the new publication. " Accordingly, Crispr-Cas9 was badumed to be reasonably accurate and the first approved clinical trials using cells thus modified are in progress ," they write. However, the badyzes made " in most of these studies " related to short areas " around potential target sites ", which " limited the scope of the evaluation ". They therefore hypothesized that these studies " might have missed a substantial proportion " of errors generated at a distance by Crispr-Cas.9

To investigate this question further, the researchers conducted a comprehensive systematic study on human and mouse cells. They discovered that Crispr-Cas9 frequently caused extensive mutations, but at a greater distance from the target site. Some of these changes were in fact too far from the target site to be observed with standard methods. Large genetic rearrangements such as unwanted deletions and insertions of portions of DNA have been observed. This type of modification could lead to the activation or deactivation of important genes, with potentially heavy consequences. The unintentional changes caused in DNA by this technique " have been largely underestimated until now ," said in a statement Allan Bradley, of the Wellcome Sanger Institute in England, where the study

Research should be continued

" Consideration of using this technique in gene therapy should be accompanied by great care, monitoring possible negative effects ", he continued. " This study emphasizes that when it comes to editing the genome, it is essential to check that the changes that occur are those and only those that we wanted to provoke.It has always been obvious ", commented a researcher who did not participate in the study, Robin Lovell-Badge, from the Francis Crick Institute in London. However, " these results do not justify panic or loss of faith in these techniques ," he continued. All researchers insist on the fact that it is necessary to continue research on Crispr-Cas9 before any clinical application.

IMMUNIZATION . From 65 to 79% of the population would be immune to the Crispr-Cas9 protein, according to a study still pre-published (still not reviewed by a committee of reading) of January 2018. And 46% of the population would also have white blood cells specifically directed against these proteins. " One possible solution is to develop a Cas9 system from bacteria that do not colonize or infect humans ," said one of the authors, Matthew Porteus, pediatric hematologist at Stanford University in California.

With AFP