Edits made by the CRISPR-Cas9 machinery, even when at the proper target, may lead to large deletions or complex rearrangements, a new study has found. As GenomeWeb has noted, these changes could be pathogenic.
Researchers from the Wellcome Sanger Institute used long-read sequencing and long-range PCR genotyping to examine the ramifications of on-target CRISPR-Cas9 genome editing. As they report in Nature Biotechnology, the researchers found that the DNA breaks induced by single-guide RNA-Cas9 led to kilobase-long deletions in about 20 percent of cells and sometimes crossover events.
"We found that changes in the DNA have been seriously underestimated before now," senior author Allan Bradley from Sanger tells Reuters.
Concerns have been raised previously about the safety of CRISPR-based gene editing, New Scientist notes. A paper published last year reportedly uncovered a number of off-target edits, though it has since been retracted. Another paper more recently has linked CRISPR editing to a risk of cancer, it adds.
The Francis Crick Institute's Robin Lovell-Badge tells Reuters that the new study suggests researchers using CRISPR need to carefully "verify that the alterations to the DNA sequence are those, and only those, that had been designed to occur."
Stat News adds that the report sent the stocks of CRISPR companies down. It notes, though, that the firms question whether the paper's findings are applicable to the types of cells they are using.