DNA damage from CRISPR/Cas9 editing could lead to cancer, finds report
A team of researchers conducted a study in both mouse and human cells, with extensive mutations found in both.
CRISPR/Cas9, a genome editing tool, can alter cell DNA at specific points by introducing changes at that location. CRISPR is being explored to potentially create treatments for HIV, cancer and sickle cell disease, by inactivating disease-causing genes.
Samantha Wynne, of the Wellcome Sanger Institute where the study was conducted, told us, “[The report] is a call for more scrutiny. We need to know what risks are involved, especially when editing hundreds of millions of cells in a therapeutic context.”
Cell mutations found in this study had not been previously reported. Researchers found that many cells had large genetic rearrangement and in some cases were far away from the target cell site.
The study states, “We report significant on-target mutagenesis, such as large deletions and more complex genomic rearrangements at the target sites in mouse embryonic stem cells, mouse hematopoietic progenitors and a human differentiated cell line.”
Wynne said, “We observed unexpected loss of gene expression when we targeted intronic regions with CRISPR/Cas9—something that would not have happened if the CRISPR editing only created small mutations. This led us to carry out thorough investigations, and we discovered large deletions and complex rearrangements that explained the initial observations.”
Wynne suggested that base editors, which does not require double-strand breaks, might reduce the risk, as they induce DNA breaks more rarely than regular Cas9.
