"Genetic magic scissors" accuracy is lower than expected

The British "Nature Biotechnology" magazine published an important study online on the 16th: the CRISPR-Cas9 genome editing technology known as "genetic magic scissors", which causes DNA deletion or rearrangement near the target, than scientists expected. It must be serious. The findings imply that researchers must closely observe sequence changes in edited cells based on CRISPR-Cas9 therapy.

Currently, the CRISPR-Cas9 genome editor has been widely recognized as a potential treatment for cancer, HIV, hemophilia and sickle cell disease. The mechanism of action of Cas9 is to cleave the cellular DNA duplex of the target site within the genome. The path of cell repair DNA double-strand breaks usually introduces small-scale DNA insertion or deletion. This process can be used to inactivate disease-causing genes or to correct genetic mutations. Prior to this, the main safety concern of this technology is that Cas9 has a higher off-target rate.

But this time, Alan Bradley, a scientist at the Wellcome Sanger Institute in the United Kingdom, and his colleagues discovered that small-scale DNA, known to occur with DNA double-strand break repair, was discovered by studying mouse and human laboratory cell lines. False, CRISPR-Cas9 technology may also cause large-scale DNA deletion near the target, and in some cases, even cause complex DNA rearrangements.

The team found that in mouse stem cells and human retinal pigment epithelial cells, deletions of thousands of DNA bases may occur, leading to adjacent genes or regulatory sequences that may be affected and alter cell function.

The researchers said that the correlation between the above findings and the clinical application of Cas9 is not known. Although the original purpose of the above experiments was not to detect the deleterious effects of chromosomal changes other than knocking out target genes, it highlighted a potential safety hazard and further research is urgently needed.

Just in February of this year, the Nature website also reported a study led by Stanford University, which revealed that the body's own immune system may also destroy gene therapy based on CRISPR-Cas9. (Reporter Zhang Mengran)

Editor-in-chief

This is another unexpected gain in the study. Although it was not for the discovery of hidden dangers, the researchers unexpectedly discovered the effect of “genetic magic scissors”, which is “cutting and chaos”. In a sense, this study is a reminder that researchers need to be more cautious and face the limitations of all new technologies. However, the academic community and the industry do not have to feel that the CRISPR-Cas9 is "cool" because of this "negative" effect. Of course, don't ignore the problem. Filling out the exposed defects one by one, and letting the emerging technologies continue to improve, the "genetic magic scissors" is still the "children of tomorrow" on the road to human beings.


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