Study shows that CRISPR-Cas 9 genome editing can be perfectly safe in mice.

With so much being written on why we should, or shouldn’t, employ CRISPR for germline editing, a new study published in Nature Methods has shown that some of those safety concerns might be easier to overcome than previously thought.

A whole-genome study was carried out on the offspring of mice born from an embryo modified using CRISPR-Cas9. Results failed to find significant off-target mutations that could be linked to CRISPR. While variations were identified, none appeared to be in a true off-target site, and were concluded to have arisen spontaneously.

“CRISPR technology is much safer than we have been led to believe from studies in cancer cell lines,” says Dr William Skarnes, a senior author from the Wellcome Trust Sanger Institute. “When we used CRISPR-Cas9 in normal mouse embryos, we observed no unexpected damage. Future studies addressing CRISPR specificity and off-target mutations will need to focus on normal embryos or cells.”

The consensus has been that using Cas9 nickases would be far safer due to the extremely low probability of error. As nickases work in pairs, the probability of identical errors is extremely low. These results suggest that difference might not be as big as people think. “There is very little difference between using wild-type Cas9 and nickases,” says Dr Vivek Iyer first author from the Sanger Institute. “We found only one highly-related site damaged in Cas9-treated mice, compared to no damage at all in nickase-treated animals. One drawback of the nickase approach is we’re depending on two incredibly precise events happening at the same time, so there is a greater chance that the experiment will fail. We’ve shown in this research that wild-type Cas9, which can reach more of the genome, can be just as safe.”

If CRISPR’s safety can continue to be demonstrated in animal models, it could be of great benefit to researchers, and mice. “This technology presents us with an incredible opportunity,” says Professor Allan Bradley, Director Emeritus at the Sanger Institute and pioneer of the embryonic stem cell technology used to produce mouse mutants. “If we can show, as these results begin to, that CRISPR can be used safely, we could improve the efficiency of breeding and reduce animal use dramatically while still empowering research.”

This is where the story starts to tie up with much of what you will have been reading over the last few months. Increased safety and efficiency in animal models is very useful for the sake of creating better models, but at some point research will look beyond animals and into what other impact CRISPR might have. “The potential of CRISPR is enormous,” says Dr Xingxu Huang, a senior author from Nanjing University currently working in ShanghaiTech University. “It is already transforming drug discovery; if we can continue to demonstrate its safety and efficiency in animal models, we can begin to think about the impact the technology could have in human medicine.”


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