CRISPR May Increase Cancer Risk in Cells

CRISPR (Credit: Ernesto del Aguila III, NHGRI)

CRISPR-Cas9 may inadvertently increase cancer risk in treated cells, according to a new study from researchers at Cambridge University and the Karolinska Institutet. The research, published in Nature Medicine yesterday, found that the gene editing technique could induce the activation of a mechanism associated with DNA damage that leads to cell death, hindering CRISPR activity. This activation meant that cells without a functional DNA repair system preferentially survived editing and thus the population of edited cells was skewed towards the damaged cells.

In May last year, a study published in Nature Methods raised concerns  that the CRISPR-Cas9 system may be causing hundreds of unintended edits in cells and, as a result, the technique could pose much greater risk than previously believed. The scientific community was initially rocked by this report, but many critics were quick to point out the flaws in the study and subsequent research disproving their findings put the matter to rest this February.

Nonetheless, the publication of the initial paper last year was indicative of how uncertain researchers are about the safety of CRISPR. To further investigate these concerns, researchers from the University of Cambridge, UK, and the Karolinska Institutet, Sweden, worked together to observe how the technique affected the risk of cancer in cells.

Gene Editing 101: 2018 Edition

The team found that when CRISPR was used in healthy cells, the gene editing activity triggered a p53-mediated DNA damage response that ultimately led to cell death. In cells which had a malfunctioning p53 pathway, a status that has long been associated with cancer pathogenicity, the intended gene editing was much more successful as there was no hindrance. Because of this inequality in editing rates, the resulting edited cell population contained a much higher proportion of cells without a p53 pathway. Without this DNA repair mechanism, the cells are at a much greater risk of developing cancerous mutations and as such, the edited cells are less stable than the initial population.

“Although we don’t yet understand the mechanisms, we believe that researchers need to be aware of the potential risks when developing new treatments,” said Jussi Taipale, PhD, team leader and Professor of Biochemistry at the University of Cambridge. “This is why we decided to publish our findings as soon as we discovered that cells edited with CRISPR-Cas9 can go on to become cancerous.”

However, the team is also keen to ensure that their work doesn’t deter researchers from investigating and using the gene editing tool.

“CRISPR-Cas9 is a very promising biological tool, both for research purposes and for potential life-saving medical treatments, and so has understandably led to great excitement within the scientific community,” said Professor Taipale. “We don’t want to sound alarmist, and are not saying that CRISPR-Cas9 is bad or dangerous. This is clearly going to be a major tool for use in medicine, so it’s important to pay attention to potential safety concerns. Like with any medical treatment, there are always side effects or potential harm and this should be balanced against the benefits of the treatment.”

This may be the reason the US Food and Drug Administration put a planned human CRISPR trial on hold before it even started, last month. 

The FDA placed the hold “pending the resolution of certain questions that will be provided by the FDA as part of its review,” the press release said.