Jul 16, 2018

CRISPR editing may cause more DNA damage than expected

Illustration of DNA molecule with edits.

Illustration: Rebecca Zisser/Axios

The gene editing tool CRISPR-Cas9 may cause large deletions and rearrange the DNA it is targeting in some cases, according to a new U.K. study published in Nature Biotechnology Monday.

Why it matters: Scientists hope CRISPR can one day be used to treat cancer, HIV, haemophilia and sickle cell disease. But this and other recent studies find it can cause unintended edits, and possibly trigger cancer.

"The DNA chaos that CRISPR unleashes has been 'seriously underestimated,'” study author and geneticist Allan Bradley of U.K.'s Wellcome Sanger Center tells STAT. “This should be a wake-up call.”

What they did: The three scientists edited two types of mouse cells and human cells and sequenced long stretches of the DNA in the edited sections.

What they found: Deletions of up to several thousand DNA bases were seen, along with complex rearrangements at the target site, which means neighboring genes could be affected or cell function altered, the authors said.

  • In one experiment, they found two-thirds of the edited genes showed expected levels of small unwanted changes, but 20% of them had large unplanned deletions.
  • "As genetic damage is frequent, extensive and undetectable by the short-range PCR assays that are commonly used, comprehensive genomic analysis is warranted to identify cells with normal genomes before patient administration," the authors warned in their study.
  • Yes but: Patrick Hsu, principal investigator and Salk Helmsley Fellow at the Salk Institute for Biological Studies, tells Axios in an emailed statement, "It’s worth noting that the large deletions found in this study are still in the single digit kilobase range, so they are still mostly local events that may not necessarily affect neighboring genes."

More reactions:

  • “I do believe the findings are robust,” Gaetan Burgio of the Australian National University, who has debunked previous studies questioning the method’s safety, tells New Scientist. “This is a well-performed study and fairly significant.”
  • Very careful work is needed “to verify that the alterations to the DNA sequence are those, and only those, that had been designed to occur,” stem cell expert Robin Lovell-Badge told Reuters.“But the results give no reason to panic or to lose faith in the methods when they are carried out by those who know what they are doing.”

What's next: "This study raises important parameters that should be tracked and monitored for therapeutic applications. There are clear paths forward for each of these potential challenges, but both the challenges and solutions are still at the blackboard level. We won’t necessarily know their relative importance until we are in the clinic," says Hsu, who was not part of this study.

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