Scientists and biotechnologists have heralded the CRISPR-Cas9 gene editing system as revolutionary way to edit DNA, like scissors and a glue stick for the genome. But a new study found some potentially harmful unintended effects.
This isn’t the first time a paper has found flaws in CRISPR’s abilities, though one previous paper on the matter has been retracted. But many feel this new research is worth taking seriously, and that CRISPR might cause large, unexpected deletions to a cell’s genome.
“We speculate that current assessments may have missed a substantial proportion of potential genotypes generated by on-target Cas9 cutting and repair, some of which may have potential pathogenic consequences following somatic editing of large populations of mitotically active cells,” the authors of the study from the Wellcome Sanger Institute in the United Kingdom write in the paper published this week in Nature Biotechnology. Basically, past research may have missed lots of CRISPR’s potentially harmful consequences.
CRISPR-Cas9 is a gene-editing system developed this past decade from a bacterial self-defense system. It provides a way to accurately cut a target strand of DNA in order to delete or replace base pairs, the pairs of As, Cs, Ts, and Gs that comprise the genetic code. It’s become popular in research and there are already clinical trials studying the use of CRISPR-Cas9 edited cells as therapies for disease.
The new research demonstrates some drawbacks to the system, and proposes that it hasn’t been studied enough in cells that can fix their own DNA. The scientists tried removing a gene in male mouse embryonic stem cells, and in many cases, large chunks of DNA, perhaps thousands of base pairs long, went missing.
The researchers point out that this damage might be undetectable by some commonly used methods to amplify and sequence DNA. On top of that, when using billions of edited cells in a therapy, it’s possible that some resulting cells will have detrimental, even cancer-causing properties. The damage might be bad enough such that, when using CRISPR-edited cells in therapies, “comprehensive genomic analysis is warranted to identify cells with normal genomes before patient administration,” according to the paper.
Synthetic biologists not involved with the study felt it was important. “I thought it was a rigorous proof-of-concept study,” Ravi Sheth, graduate student in synthetic biology at Columbia told Gizmodo. He said the study demonstrated that newer sequencing strategies that look at longer strands should be used to help figure out where CRISPR could have gone wrong, and that scientists need to work on strategies to stop the cell from trying to fix DNA on its own.
Gizmodo also reached out to biotechnologist George Church, who pointed us toward a STAT News article where he said, essentially, that he wasn’t surprised and that he and his lab are working on ways to edit DNA without breaking both strands of the double helix. Church likened this to gene vandalism versus gene editing—breaking both strands is more likely to cause these errors.
The new study caused three CRISPR companies to lose a combined $300 million in the 20 minutes after the paper’s release, STAT News reported. Spokespeople for those companies gave varying responses, some saying they hadn’t seen these effects in their own tests or in other gene-editing methods, or that the study didn’t specifically impact their work.
A new technology will inevitably have some negative side effects—and it’s better to figure them out now, before trying to gene edit living humans.