Gene-editing technique scientists hope will cure cancer and all inherited disease found to have dangerous flaw
"We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by Crispr."
It has been hailed as a cure for cancer and all forms of inherited disease.
But scientists have now discovered that a system for editing the genes of living creatures can have a potentially dangerous side-effect - causing unintended mutations.
Writing in the journal Nature Methods, researchers in the US described how they had used Crispr-Cas9 to restore sight to blind mice.
However, when they then sequenced the entire genome of the animals, they found two had more than 1,500 small mutations and more than 100 larger deletions and insertions of genetic material.
One of the researchers, Professor Stephen Tsang, of Columbia University, said: "We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by Crispr. Researchers who aren't using whole genome sequencing to find off-target effects may be missing potentially important mutations. We hope our findings will encourage others to use whole-genome sequencing as a method to determine all the off-target effects of their Crispr techniques and study different versions for the safest, most accurate editing."
He added that even a small change – even affecting a single nucleotide, the basic building block of DNA – could have a "huge impact".
Previously, scientists have used a computer algorithm to highlight areas of the genome most likely to have been damaged inadvertently and then examine those sections of DNA alone.
The researchers said these algorithms "seem to do a good job" when Crispr was used on tissues in the laboratory, but full genome sequencing was required when dealing with live animals.
And the researchers said they were still confident that gene-editing would be medically useful.
Professor Vinit Mahajan, of Stanford University, who also took part in the research, said: “We're still upbeat about Crispr.
"We're physicians, and we know that every new therapy has some potential side effects – but we need to be aware of what they are."
They are now trying to improve the targeting and cutting techniques used by the Crispr system.
