New research shows CRISPR gene editing can create potential adverse side effects. The study by Sanford Burnham Prebys Medical Discovery Institute, researchers at the National Cancer Institute’s Center for Cancer Research, and a list of co-authors published in Nature Communications recommended caution for CRISPR gene editing in cancer treatment.
According to the study’s authors, gene knockout (KO) with CRISPR-Cas9 appears to disproportionately favor cells with mutated genes that may be prone to cancer.
“Our study shows that in many different cell types, CRISPR gene-editing can confer a selective advantage to cells harboring mutations in genes associated with cancer, such as p53 and KRAS,” said Deshpande, Ph.D., an assistant professor in the NCI-Designated Cancer Center at Sanford Burnham Prebys in a news release. “We have shown that when CRISPR-Cas9 is used to edit the genome, cells with cancer-associated mutations are likely to be selected to survive —and this is more widespread than scientists previously understood.”
The p53 gene plays a crucial role because it prevents cell division if a genome error occurs. The gene attempts to correct the problem. However, if the error cannot be fixed, the p53 gene will launch a sequence to kill the cells before they become cancerous. If the p53 gene is impacted and unable to function properly, it can make people more susceptible to tumors, according to the study.
The study examined nearly 1,000 human cell lines and found that in almost every cell type, cells with normal p53 genes grew more slowly after CRISPR gene editing (CRISPR-Cas9 KO). Cells with mutated p53 genes were less affected, which allowed them to grow faster and outcompete normal cells in the host.
Researchers concluded that CRISPR gene editing can accelerate cells with cancer mutations, such as the KRAS oncogene.
The authors recommend a cautious approach to the use of CRISPR gene editing therapies — especially in the treatment of patients that demonstrate an underlying mutation in p53 or KRAS genes.
“There are CRISPR therapies being developed to correct mutations in many human tissues, but as others have noted before, we need to proceed with caution, because we may be selecting for cells that carry mutations in key cancer driver genes when using CRISPR-Cas9 editing, and that could be potentially dangerous,” said Eytan Ruppin, Ph.D., chief of the Cancer Data Science Laboratory at the NCI Center for Cancer Research. “However, fortunately and importantly, additional new CRISPR editing techniques that have been recently developed are much less likely to carry this risk, if at all.”
While early CRISPR gene editing produced double-stranded breaks, Deshpande points out the more modern iterations are making simpler edits when targeting DNA. A non-cutting version of CRISPR is, therefore, more likely to avoid these problems.
Despite the risks identified in the study, the authors still believe that CRISPR gene editing remains an innovative approach and that solutions are not insurmountable. The authors point out that emerging treatments often face barriers before they are deemed safe for widespread adoption.