Following reports of collateral damage caused by CRISPR genome editing, now chromothripsis, a phenomenon associated with cancer, enters the spotlight.
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October 18, 2021 2:16 AM
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CRISPR therapies are increasingly being developed. However, a recent study has identified a new danger associated with CRISPR-Cas9-based therapies. The double-stranded DNA breaks introduced during CRISPR editing could lead to chromothripsis, an extremely damaging form of genomic rearrangement that results in the breakup of individual chromosomes and the subsequent reassembly of the pieces in a disordered order. Although most cells do not remain viable after undergoing such radical modification, those that do can, in theory, express oncogenic fusion proteins or result in the deregulated expression of particular genes that can cause problems. Other studies have reported CRISPR-Cas9-induced DNA deletions and large-scale chromosomal rearrangements, CRISPR-Cas9 activation of the tumour suppressor protein p53, which could select for inactivating and cancer-causing mutations, and the induction of large chromosomal truncations. In addition, the presence of pre-existing antibodies and T cells directed against Cas9 enzymes in large percentages of the population could compromise efficacy. However, base and primer editing methods, which use single strand nicks rather than double strand breaks to introduce a modification, are much less likely to cause chromothripsis.