Scientific Advances: Chromosomal havoc following on-target Cas9 activity

Chromothripsis is a mutational process resulting in extensive chromosome rearrangement of one or a few chromosomes that can cause human congenital disease and cancer. A new study published in Nature Genetics shows that CRISPR/Cas9 editing can generate structural defects of the nucleus, micronuclei and chromosome bridges, which initiate chromothripsis. In actively dividing cells, using CRISPR to initiate double-strand breaks increased the formation of chromosomal aberrations up to 20 times. This study flags a new concern with on-target CRISPR editing that will need to be monitored and further studied, despite a lack of evidence of malignant transformation from CRISPR studies thus far.

For more information, see: Leibowitz, M.L., et al. (2021) Chromothripsis as an on-target consequence of CRISPR/Cas9 genome editing. Nat. Genet. https://doi.org/10.1038/s41588-021-00838-7

Keywords: CRISPR, DNA damage, chromothripsis

Questions? Email: crispr@amsterdamumc.nl