Researchers Discover Hundreds of Unexpected Mutations from New Gene Editing Technology

For the past few years, a new scientific tool known as CRISPR-Cas9 has been hailed as the future of medicine. The technology, which has been the center of both extreme fascination and a bitter patent dispute between two research groups, enables scientists to edit genomes. That is, they can remove harmful genes that cause diseases and replace them with normal genes that don't—at least in theory. While exciting to many, the idea has also elicited fears that the technology could create dangerous mutations and be used in unbridled ways, for example in attempts to create superhumans and designer babies.

According to a new report, such fears may be well founded. The study, published in Nature Methods , found that using CRISPR-Cas9 to edit a genome can result in hundreds of unintended mutations being introduced. For the report, researchers sequenced the genomes of mice that had already undergone CRISPR-Cas9 procedures. They then scrutinized the edited genomes for any changes in the mouse genes—and they found plenty. The technology had accomplished the original intended task of correcting a gene that causes blindness, but it had also resulted in 1,500 other small changes and 100 large changes. Not one of those changes had been predicted by the researchers.

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The small changes were what are known as single-nucleotide mutations. With these alterations, just one nucleotide—that is, the chemicals known as A, T, G, and C that make up the building blocks of DNA—switches to a different one. But even that tiny change can have a big effect: single-nucleotide mutations are involved in many diseases.

"We're still upbeat about CRISPR," Vinit Mahajan, who researchers ophthalmology at Stanford University and co-authored the study, said in a statement. "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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Meanwhile, the first clinical trials to study CRISPR-Cas9 in humans have begun. Last October, researchers at Sichuan University in China injected genetically modified cells into the first of 10 lung cancer patients. At the University of Pennsylvania, a study to edit genes in cells from patients with several types of cancer, including melanoma and myeloma, has been approved by the National Institutes of Health. And researchers at Peking University, in Beijing, are awaiting approval for their study of CRISPR-Cas9 to treat bladder cancer and prostate cancer.

Whatever the future of CRISPR-Cas9 may be, it will no doubt be tightly regulated. The approach so far is not only untested but also raises important ethical concerns. The discovery of unexpected consequences in this mouse study is sure to add fuel to that laboratory fire.

Jennifer Doudna, molecular biologist at University of California, Berkeley, explains CRISPR-Cas9 gene-editing technology at the 2016 Milken Institute Global Conference in Beverly Hills, CA, May 2016. A new study found unexpected mutations in mice that underwent a CRISPR-Cas9 procedure. Frederic J. Brown/AFP/Getty Images

Jennifer Doudna, the molecular biologist at the University of California, Berkeley, who co-discovered CRISPR-Cas9, sees no cause for concern. "I don't think any conclusions can be drawn from the work," she says. The study used the technology in a different way than is employed by the vast majority of labs, says Doudna, and the alternative approach could have been responsible for the unexpected mutations. That assertion is supported by the fact that none of the genome sites that prior research highlighted as most susceptible to accidental mutations due to CRISPR-Cas9 were affected. Doudna also says the statistical analysis reported in the paper "does not hold up to rigorous scrutiny."