One of the first in-depth looks into the impact of CRISPR/Cas9 is raising questions regarding the safety of the gene editing tool.
Previous research had not shown many unforeseen mutations from CRISPR/Cas9 in the DNA at the genome editing target site. Scientists from the Wellcome Sanger Institute carried out a full systematic study in both mouse and human cells and discovered that CRISPR/Cas9 frequently caused extensive mutations away from the target site. This discovery that could create safety implications for gene therapies in the future from unexpected damage in some cells.
CRISPR/Cas9 has been used to alter sections of DNA in cells by cutting at specific points and introducing changes at their location. The new gene editing tools could lead to new treatments for a variety of diseases including HIV, cancer and sickle cell disease.
While these therapeutics could inactivate a disease-causing gene or correct a genetic mutation and scientists have long believed that the tools were reasonably specific, they have yet to be proven completely safe.
“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,” professor Allan Bradley, corresponding author on the study from the Wellcome Sanger Institute, said in a statement. “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.”
The team found that many of the cells had large genetic rearrangements such as DNA deletions and insertions, which could lead to important genes being switched on or off. This could have implications as to whether CRISPR/Cas9 should be used in therapies.
The researchers also found that some of the changes were too far away from the target site to be seen with standard genotyping methods.
“My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however it became clear that something unexpected was happening,” Michael Kosicki, the first author from the Wellcome Sanger Institute, said in a statement. “Once we realized the extent of the genetic rearrangements we studied it systematically, looking at different genes and different therapeutically relevant cell lines, and showed that the CRISPR/Cas9 effects held true.”
The study was published in Nature Biotechnology.