From the promise of malaria-free mosquitos to a potentially limitless supply of transplant organs or cures for some of humanity’s worst diseases, CRISPR-Cas9 gene editing sounds almost too to be true. Unfortunately, at least according to researchers in the United Kingdom, that could turn out to be true. In a recently published Nature paper, researchers from the Wellcome Sanger Institute — a nonprofit British genomics and genetics research institute — warn that gene editing has the potential to end badly. Specifically, they are worried that DNA alterations could result in cells turning cancerous.
Their conclusions are based on studying two genes in different cell types in the form of mouse embryonic stem cells and human immortalized cells. By studying these genes, they observed that genomic damage was a “common outcome.”
“Many researchers assumed that the repair of Cas9-induced DNA breaks results only in local changes of a few to few hundred DNA bases,” Michael Kosicki, a researcher at the Wellcome Sanger Institute, told Digital Trends. “This is often the intended result and even as a side effect, it is not expected to be especially harmful. We have found that large deletions of thousands of bases and complex rearrangements are another frequent outcome. Both are difficult to detect using standard methods and may have consequences beyond the intended ones.”
The idea of CRISPR technology causing something akin to genetic typos is unsettling, but Kosicki notes that this isn’t just the stuff of alarmist Michael Crichton-style sci-fi warnings about the future. In fact, gene editing has led to damaging results before, when early gene therapy trials a decade and a half ago led to the accidental activation of a gene that caused cancer.
“Gene therapy often involves editing of hundreds of millions of cells and even one cell can potentially initiate a neoplasm,” he continued. “This is why ‘off-target effects’, the potential for Cas9 to mistakenly target another gene, were taken so seriously by the gene editing community. We believe ‘on-target effects’ should as well. [It may also] depend on the targeted gene. Some places in the genome may be more likely to be at risk, especially if they are close to oncogenes.”
Kosicki said that the research institute’s paper is a “call for more scrutiny and caution” when deploying CRISPR-Cas9 technologies in the future. “The changes we described can be easily detected, if you know what you are looking for,” he said. “In some cases, this additional risk may be worth the potential benefit; in some, it will not. More knowledge will make regulators’ choices more informed.”
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