New tools of genome editing introduce undesirable mutations

Genome editing in recent years has become synonymous to CRISPR toolset. However, we are still not certain about the accuracy and efficiency of procedures involving Cas enzyme. New research suggests that seemingly precise single base editing isn’t so precise after all – and introduced various unwanted changes during trials.

The experiments aimed to assess off-side (off-target) effects of cytosine base editors (converting C to T in DNA) and adenine base editors (converting A to G). Those enzymes hold great promise to precisely correct single-base mutations, which cause thousands of diseases.

Analyses of edited rice plants and mouse embryos revealed significant off-target changes in case of cytosine base editors.

Researchers found 283 new mutations after editing, in contrast with 12 identified after control procedure using Cas enzyme without cytosine base editing capability. Moreover, 14 of new mutations were found in genes associated with cancer risk, which constitutes the oncogenic risk of this specific tool.

Source & more: Cytosine base editors go off-target, doi:10.1038/s41576-019-0110-x.