Side effects of CRISPR lead to hundreds of unintended mutations

30 May 2017

Image: vchal/Shutterstock

Few technologies are as revolutionary as the CRISPR genome editing method, but a new study finds that it could be creating hundreds of unintended mutations.

Mention the acronym CRISPR to anyone who follows the latest developments in sci-tech and you will likely hear many opinions, ranging from prophecy to downright condemnation.

Unlike anything before it, CRISPR is a technology that has proven effective in slicing out harmful genomic sequences in DNA, with the purpose of one day being able to remove harmful diseases from a human’s make-up.

Its testing remains highly controversial, as China alone has confirmed its first trials using the method on human embryos, with limited trialling elsewhere soon to begin.

Now, however, research conducted by Columbia University Medical Center has revealed startling evidence that CRISPR creates hundreds of unintended mutations in the genome.

Published in Nature Methods, the research looked at sequencing the entire genome of mice that had previously undergone CRISPR gene editing, and analysed any mutations down to a single nucleotide.

While the team identified that CRISPR had corrected the gene that leads to blindness in mice, PhD student Kellie Schaefer found that hundreds of genes had been altered.

Within the genomes of two independent gene therapy subjects, Schaefer found more than 1,500 single-nucleotide mutations and more than 100 larger deletions and insertions, none of which had been predicted during computer simulations.

Need for whole-genome sequencing

“These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole-genome sequencing has not been employed to look for all off-target effects in living animals,” said study co-author Alexander Bassuk.

The findings are likely to reignite ethical and scientific debate surrounding the controversial method, with the first US trial scheduled to take place in the beginning of 2018.

In the meantime, researchers are continuing to improve the components of the CRISPR system and boost the editing efficiency through its gene-cutting enzyme.

Co-author Stephen Tsang added: “We hope our findings will encourage others to use whole-genome sequencing as a method to determine all the off-target effects of their CRISPR techniques and study different versions for the safest, most accurate editing.”

Colm Gorey was a senior journalist with Silicon Republic