CRISPR/Cas9 is a type of molecular scissor technology that can alter sections of DNA in cells by cutting at specific points and introducing changes at that location.
Besides extensive use in scientific research, CRISPR/Cas9 has also been seen as a promising way to create potential genome editing treatments for diseases such as HIV, cancer or sickle cell disease.
But the new research, reported in the journal Nature Biotechnology, revealed that CRISPR/Cas9 frequently caused extensive mutations, though at a distance from the target site.
Many of the cells, in both mice and humans, had large genetic rearrangements such as DNA deletions and insertions.
These could lead to important genes being switched on or off, which could have major implications for CRISPR/Cas9 use in therapies.
In addition, some of these changes were too far away from the target site to be seen with standard genotyping methods, the researchers said.
"This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now," said Allan Bradley, Professor at the Wellcome Sanger Institute in London.
"It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects," Bradley added
The work has implications for how CRISPR/Cas9 is used therapeutically and is likely to re-spark researchers' interest in finding alternatives to the standard CRISPR/Cas9 method for gene editing.
"While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically," the researchers said.
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