CRISPR is in doubt again
The popular DNA editing method has proved deadly
Scientists from the Sanger Institute (UK) have found that the use of the CRISPR/Cas system in human and animal cells, including mice, often leads to the appearance of extensive undesirable mutations. These damages in the genome are not detected by standard DNA genotyping methods. The researchers' article was published in the journal Nature Biotechnology (Kosicki et al., Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements). This is reported by the publication Science Alert.
The CRISPR/Cas system is used to change the nucleotide sequence of DNA. Cas is a protein that cuts a double chain at a certain site. This location is determined by the guide RNA (sdRNA), which binds to a specific recognition site on the principle of complementarity. Various sdRNAs are encoded by spacers – DNA regions located within the CRISPR group of special repeating sequences.
Sometimes Cas cuts off quite large nucleotide sequences (their length can reach hundreds of bases), but it is believed that such side effects are quite rare. The CRISPR/Cas system has thus been approved for a number of clinical trials, including T-cell modification for the treatment of esophageal cancer, leukemia and non-small cell lung cancer.
In May 2017, a team of scientists from Columbia University announced that CRISPR/Cas9 makes many changes to DNA outside of the desired site. Although the researchers were unable to confirm their own results, other scientists have also received evidence that the CRISPR system causes more side effects than previously thought.
In the new work, scientists evaluated the effect of CRISPR on mouse stem cells and human retinal epithelial cells. It turned out that the system caused large-scale genetic rearrangements, including deletions (loss of chromosome sections) affecting several thousand base pairs away from the site that was directly edited with CRISPR. Such mutations can irreversibly damage important genes, which is deadly for patients who may receive gene therapy.
Even if only one of the millions of cells carries pathogenic mutations, there is a serious risk of developing cancerous tumors. Scientists believe that further research is needed in order to understand how to prevent editing errors.
Portal "Eternal youth" http://vechnayamolodost.ru