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Experts criticized the article about the side effects of CRISPR/Cas9

Oleg Lischuk, N+1

Experts from Intellia Therapeutics and Editas Medicine, who are developing the CRISPR/Cas9 genome editing technology, sharply criticized a recent publication in the journal Nature Methods, which talks about numerous non-targeted mutations when using this technology. They present their arguments in two independent statements (one and two).

The authors of the original publication sequenced the complete genome of two mice to which they had previously corrected a genetic defect leading to blindness at the zygote stage using CRISPR/Cas9. They compared the results obtained with the data of a genome-wide analysis of a control animal that had not been edited by genome editing. According to the results of the study, the scientists concluded that the use of the technology led to the emergence of many non-target mutations: 1,397 single-nucleotide substitutions and 117 insertions and deletions, which significantly exceeds previous estimates of the side effects of CRISPR/Cas9.

This publication and a press release dedicated to it by Columbia University in New York caused considerable media excitement, which led to a drop in stock prices of companies engaged in developments in the field of genome editing, including Intellia and Editas.

In their response statements, the experts of the companies draw attention to numerous shortcomings in the design of the study. In particular, they point out that its authors did not sequence the genome of the parents of animals in which CRISPR/Cas9 was used, namely, this would make it possible to assess with sufficient accuracy the contribution of technology to the detected genetic differences. Critics also note that previous similar studies using genome-wide analysis have not found a similar number of side effects of the technology, and the genetic differences between experimental animals and control animals fit into the range of natural differences between mice of the same line. Moreover, some of the registered mutations go beyond the capabilities of CRISPR/Cas9. Thus, the results obtained do not allow us to talk about a clear connection of the detected mutations with the use of technology. Among the shortcomings of the publication, errors in the identification of genes and insufficient number of experimental animals to obtain statistically reliable results are also indicated.

According to MIT Technology Review, many other scientists have made similar claims to the work.

"In our opinion, the conclusions of the study are not justified by the results of the experiments conducted," Editas said in a statement. One of its authors, co-founder of the company and Harvard professor George Church, said that the publication may need to be withdrawn, or at least supplemented with a comment on the main unaccounted-for problems.

Intellia Executive Director Nessan Bermingham took a tougher stance: "This publication attracted close attention from the press and the public, which led to significant damage. Given the questions about the design [of the study] and the interpretation [of the results], I think that the editorial board of Nature Methods should withdraw the article."

A representative of Springer Nature, the publisher of the journal, said that the editorial board has already received a number of letters concerning the publication, and is currently conducting its own proceedings, involving its authors in the discussion.

A thorough study of the potential side effects from the use of CRISPR/Cas9 is becoming increasingly important, given that its clinical trials are already underway in China and are scheduled for 2018 in the United States.

Portal "Eternal youth" http://vechnayamolodost.ru  13.06.2017