Researchers analysed thousands of laboratory-made plasmids and discovered that nearly half of them had defects, raising questions of experimental reproducibility.
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A recent study has identified another potential hazard for developers of genome editing therapies based on CRISPR–Cas9. The double-strand DNA breaks introduced during CRISPR editing could result in chromothripsis, an extremely damaging form of genomic rearrangement that results from the shattering of individual chromosomes and the subsequent rejoining of the pieces in a haphazard order. Although most cells do not remain viable after undergoing such a dramatic alteration, those that do could, in theory, express oncogenic fusion proteins or give rise to dysregulated expression of particular genes that could cause problems.
So far, none of the companies leading the clinical development of CRISPR-based therapies appears to have considered the issue; its clinical implications, if any, remain unclear. However, the study, led by Mitchell Weiss of St. Jude Children’s Research Hospital and David Pellman of the Dana–Farber Cancer Institute and Harvard Medical School, adds another layer of complexity to gene-editing’s already relatively complicated mechanism of action. “Most importantly, it’s an on-target effect. You cannot make this go away by making the cutting more specific,” says Pellman.
The study is the...