A new systemic study by Wellcome Sanger Institute in the UK has associated CRISPR/Cas9 gene editing with higher genetic damage than was previously thought.
Conducted in mouse and human cells, the study demonstrated frequent and extensive mutations with CRISPR/Cas9 at a greater distance from the genome editing target site.
Most of the cells showed substantial genetic rearrangements, including DNA deletions and insertions, which can result in critical genes being switched on or off.
According to scientists at the Institute, the study results indicate the need for safety implications with genetic therapies using CRISPR/Cas9 in the future to avoid unexpected damage that can cause harmful effects.
The team further observed that conventional detection tests for DNA changes cannot identify this genetic damage, thereby creating requirement for specific testing of potential gene therapies.
Wellcome Sanger Institute professor Allan Bradley 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.
“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.”
CRISPR/Cas9 is a genome editing tool designed to modify DNA sections in cells through cuts at specific points, where changes are introduced.
The technology is used in scientific research and expected to offer means for the development of potential genome editing therapies for various diseases such as cancer, HIV and sickle cell disease.
It is believed that genome altering therapeutics could possess the capability to correct a genetic mutation or inactivate the gene responsible for the disease.
The study was published in the journal Nature Biotechnology.
Lead author from the Wellcome Sanger Institute Micahel Kosicki said: “My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however it became clear that something unexpected was happening. Once we realised 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.”