Known as gene scissors, the CRISPR/Cas technology is considered to be the future savior against hereditary diseases. In cases of, e.g., sickle cell anemia, muscular dystrophy, and other diseases, it is said to have already produced a cure. Now, however, scientists are warning of side effects that are likely to be serious.

The study was led by Dr. Adi Barzel of the School of Neurobiology, Biochemistry and Biophysics at Tel Aviv University's Wise Faculty of Life Sciences and the Dotan Center for Advanced Therapies, together with Dr. Asaf Madi as well as Dr. Uri Ben-David of TAU's School of Medicine and the Edmond J. Safra Center for Bioinformatics. To investigate the extent of potential damage, the researchers replicated an experiment conducted in Pennsylvania in 2020, in which researchers applied the CRISPR/Cas technique to human T cells at that time. The Tel Aviv scientists edited the genome of T cells at exactly the same locations - chromosomes 2, 7, and 14 of the 23 pairs of chromosomes in the human genome. Using a state-of-the-art technology called single-cell RNA sequencing, they analyzed each cell individually and measured the expression levels of each chromosome in each cell.

The team found a significant loss of genetic material in more than 9% of the cells. According to the results, the cause of the difference in damage was the site of cleavage by CRISPR/Cas. A not inconsiderable percentage of the cells were unable to repair a chromosome break, which in turn can lead to cancer.

The scientists recommend alternatives to this technology or at least filter out the damaged cells before using them as a therapeutic agent.

The findings were published on June 30, 2022, in Nature Biotechnology.
Nahmad, A.D., Reuveni, E., Goldschmidt, E., et al. (2022). Frequent aneuploidy in primary human T cells after CRISPR-Cas9 cleavage. Nat Biotechnol. https://doi.org/10.1038/s41587-022-01377-0

Sources and supplementary information:
https://www.aftau.org/news_item/crispr-therapeutics-can-damage-the-human-genome-tau-researchers-warn/
https://www.wissensschau.de/genom/genschere_crispr-cas_therapie.php
https://www.mpg.de/11033456/crispr-cas9-erapien