CRISPR gene editing can yield hundreds of accidental mutations

"We’re physicians, and we know that every new therapy has some potential side effects -- but we need to be aware of what they are," said Dr. Vinit Mahajan, a Stanford ophthalmologist.
By Brooks Hays  |  May 31, 2017 at 4:15 PM
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May 31 (UPI) -- CRISPR-Cas9 is the most buzzed-about gene-editing technology yet developed, allowing scientists to edit DNA faster and more accurately than alternative methods.

But it's not perfect: New research proves the technique can yield hundreds of unintended mutations.

"We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome," Dr. Stephen Tsang, a professor of ophthalmology and associate professor of pathology and cell biology at Columbia University Medical Center, said in a news release.

While CRISPR-Cas9 offers the most effective strategy yet for altering DNA, gene-editing proteins can sometimes target the wrong parts of the genome. Scientists use algorithms to search for the most likely sources of accidental deletions and insertions.

"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 Dr. Alexander Bassuk, a professor of pediatrics at the University of Iowa.

In the latest study, scientists sequenced the entire genome of mice that had undergone CRISPR gene editing. They surveyed the genome for all potential erroneous mutations, even the alteration of a single nucleotide.

Their analysis confirmed the gene-editing method had successfully corrected a gene malfunction linked with blindness, but researchers also discovered 1,500 single-nucleotide alterations, as well as more than 100 more significant DNA deletions and insertions -- all of which algorithms failed to predict or identify.

The scientists published the results of their survey in the journal Nature Methods.

"Researchers who aren't using whole genome sequencing to find off-target effects may be missing potentially important mutations," Tsang said. "Even a single nucleotide change can have a huge impact."

CRISPR-Cas9 holds tremendous potential. CRISPR-Cas9 clinical trials are already under way in China, and the first clinical trial in the United States is set to begin this summer. The method could be used to better understand how genetic mutations yield disease and could eventually allow doctors to repair damaged genes.

But as with many promising therapies, there are risks -- risks researchers suggest need to be more thoroughly explored.

"We're still upbeat about CRISPR," said Dr. Vinit Mahajan, an associate professor of ophthalmology at Stanford University. "We're physicians, and we know that every new therapy has some potential side effects -- but we need to be aware of what they are."

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