Gene-editing tool CRISPR-Cas9 has garnered significant amounts of positive press in recent months, as the promise of gene editing could help with medicine and alter DNA for the better. But a new study suggests that CRISPR isn’t all it’s cracked up to be.
The study, published July 16 in Nature, makes the case that instead of CRISPR being thought of as a pair of “molecular scissors” (as it has been previously called), making surgical precise cuts, it may actually be “blunt” and cause more damage than previously thought.
“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,” said Allan Bradley, one of the authors of the study, 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 study was co-authored by Michael Kosicki, Kärt Tomberg and Bradley, all of the Wellcome Sanger Institute in Hinxton, U.K.
According to the study, some CRISPR (short for Clustered Regularly Interspaced Short Palindromic Repeats) edits may actually produce indels (known as deletions) at a scale of thousands of bases, or significantly more expansive than previously thought. This affects adjacent genes and could interfere or disrupt certain genetic operations that have been deemed normal.
“The cell will try to stitch things back together,” said Bradley, a mouse geneticst in an interview published to coincide with with the study. “But it doesn’t really know what bits of DNA lie adjacent to each other.”
Kosicki, Tomberg and Bradley’s findings conclude that the reason this type of damage has not been encountered before in previous studies is because damage at this scale was never allowed to occur. In effect, the cell itself is not doing what it is supposed to and that’s causing alarm for some researchers in the field.
“I do think this has been underappreciated by the field,” said Patrick Hsu, a bioengineer at the Salk Institute in La Jolla, Calif.
The results of the study hit the stock prices of some companies associated with CRISPR, according to a report in The Wall Street Journal.
Prof. Maria Jasin, who was not involved in the study, said the research shows that more work is needed. “This study is the first to assess the repertoire of genomic damage arising at a CRISPR/Cas9 cleavage site,” Jasin said in a statement. “While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically.”
Fox News has reached out to George Church, professor of genetics at Harvard Medical School and one of the inventors of CRISPR-Cas9 with a request for comment.
Previous studies often used many copies of the same thousand-pair sequence, TechCrunch reports, which allowed CRISPR to function properly and the threat of any damage was negligible. It’s only when longer strands of DNA are introduced does the level of danger rise.
“We speculate that current assessments may have missed a substantial proportion of potential genotypes generated by on-target Cas9 cutting and repair, some of which may have potential pathogenic con-sequences following somatic editing of large populations of mitoti-cally active cells,” the authors wrote in the paper.
Despite the genetic damage seen on longer DNA strands, it’s unlikely to stop or halt CRISPR’s use when it comes to gene editing, James Haber, a molecular biologist at Brandeis University in Waltham, Ma. told Nature.
“It means that when people use it, they need to do a more thorough analysis,” Haber said in the article published in Nature. “It’s generally important to know whether your mutations are as you think they are.”
CRISPR has been credited with several biological and scientific achievements in recent months, including eliminating viruses in pigs that could be harmful to people, which could lay the foundations for pig-to-human organ transplants.
The gene-editing tool has also been used to correct a disease-causing gene mutation in human embryos, preventing the mutation from passing to future generations.