Skip to main content

Scientists discover hundreds of unintended mutations in CRISPR-edited mice

CRISPR
Image used with permission by copyright holder
The revolutionary gene-editing tool CRISPR-Cas9 comes with a few caveats. That’s the conclusion of a new study by physicians at Columbia University Medical Center and the University of Iowa, who ran whole-genome sequences of CRISPR-edited animals and discovered hundreds of unintended mutations.

Discovered in the 1980s but only just turned into a remarkable tool for geneticists within the last few years, CRISPR has been celebrated as a game-changer, because scientists can use it to make safe and precise edits to specific places in the genome. The possibilities have seemed practically endless. With CRISPR, scientists can edit drought resistance into plants, edit horns out of cattle, and — maybe someday — edit disease out of human beings.

Recommended Videos

However, some scientists have decided to approach the new technology with caution.

Please enable Javascript to view this content

“As physicians, we are taught the old adage,” Alexander Bassuk, a professor of pediatrics at the University of Iowa, told Digital Trends, “‘No side effect, no effect.’”

What Bassuk means is every treatment is expected to have side effects, no matter how effective that treatment may be.

“CRISPR gene editing is a very promising technology, and we are extremely excited about testing CRISPR therapy,” he said. “We were initially motivated by trying to understand the side effects of CRISPR editing.”

In previous studies, other researchers have demonstrated that CRISPR treatments can result in unintended (or, “off-target”) mutations. However, prior studies haven’t looked for off-target effects in the entire genome, often working within the confines of a test tube and using computer algorithms to predict the unintended mutations, according to Bassuk.

“We know that the computer algorithms are excellent for predicting off-target sites that are very similar to the target site, especially when these sites are tested in a test tube,” he said. “Our approach was different in that we studied gene-edited animals and we looked at every single nucleotide base pair not just those predicted by the current algorithms.”

Bassuk and his team decided to scrutinize the organism’s entire genome. “We decided to look at mice treated with CRISPR gene editing, and to examine every single nucleotide base pair using a new whole genome sequencing method,” he said.

What Bassuk and his co-author Stephen Tsang, associate professor of pathology and cell biology at Columbia University Medical Center, discovered were more than 1,500 single nucleotide mutations and over 100 more significant deletions and insertions in two mice that underwent different gene therapies.

“It is unclear that the method we developed using whole genome sequencing is more time-consuming then predictive algorithms, but at least initially, it may be more expensive,” Bassuk explained. “However, the cost for using our method is decreasing rapidly as prices for sequencing continue to decrease.”

The researchers stills support the use of CRISPR but suggest that scientists use caution moving forward to avoid potentially harmful side effects. They see at least two big scientific take-aways from this study. First, they point to the obvious concern that at least some CRISPR edits result in unintended — and potentially impactful — mutations. Second, current computer algorithms may not be able to consistently predict these off-target mutations in live animals.

A paper detailing the study will be published in an upcoming issue of the journal Nature Methods.

Dyllan Furness
Former Digital Trends Contributor
Dyllan Furness is a freelance writer from Florida. He covers strange science and emerging tech for Digital Trends, focusing…
Hyundai Ioniq 5 sets world record for greatest altitude change
hyundai ioniq 5 world record altitude change mk02 detail kv

When the Guinness World Records (GWR) book was launched in 1955, the idea was to compile facts and figures that could finally settle often endless arguments in the U.K.’s many pubs.

It quickly evolved into a yearly compilation of world records, big and small, including last year's largest grilled cheese sandwich in the world.

Read more
Global EV sales expected to rise 30% in 2025, S&P Global says
ev sales up 30 percent 2025 byd sealion 7 1stbanner l

While trade wars, tariffs, and wavering subsidies are very much in the cards for the auto industry in 2025, global sales of electric vehicles (EVs) are still expected to rise substantially next year, according to S&P Global Mobility.

"2025 is shaping up to be ultra-challenging for the auto industry, as key regional demand factors limit demand potential and the new U.S. administration adds fresh uncertainty from day one," says Colin Couchman, executive director of global light vehicle forecasting for S&P Global Mobility.

Read more
Faraday Future could unveil lowest-priced EV yet at CES 2025
Faraday Future FF 91

Given existing tariffs and what’s in store from the Trump administration, you’d be forgiven for thinking the global race toward lower electric vehicle (EV) prices will not reach U.S. shores in 2025.

After all, Chinese manufacturers, who sell the least expensive EVs globally, have shelved plans to enter the U.S. market after 100% tariffs were imposed on China-made EVs in September.

Read more