CRISPR causes many unwanted mutations, small study suggests

By Michael Le Page

Does the CRISPR gene-editing method cause hundreds of extra, unwanted mutations? That’s the question raised by a small study in mice.

The idea of gene editing is to alter a single DNA sequence in the genome of cells while leaving the rest untouched. However, in practice, every gene-editing method sometimes results in unwanted changes.

This is not necessarily a problem if the rate of unwanted changes is low, as most mutations have no effect. But mutations in certain genes can lead to cancer, so the safety of CRISPR depends on how often it makes these off-target mutations.

Most studies have found few if any unwanted mutations with CRISPR. However, almost all of these studies looked for off-target changes by predicting what these were likely to be, and then seeing if they could find them.

Stephen Tsang of Columbia University Medical Center and his team have now used a more extensive method, sequencing the whole genomes of two CRISPR-edited mice, and comparing these with a non-edited control. In this way, they identified more than a thousand common mutations in the two edited mice that they think were caused by CRISPR.

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