CRISPR Gene Editing Research Hits a Snag
CRISPR-Cas9 gene editing technology made waves in the scientific community a few years ago, when it appeared to allow precise editing of genetic mutations. For parents-to-be who carry genetic mutations themselves, or find out that a fetus carries a dangerous genetic mutation, this technology could literally be life-saving. However, new research on possible side effects is providing a healthy dose of reality to anyone who assumed this technological feat would be a clean solution to genetic defects.
As the technology starts to move into clinical trials, a new study published in Nature Methods has found that the gene-editing technology can introduce hundreds of unintended mutations into the genome.
CRISPR-Cas9 technology — by virtue of the speed and unprecedented precision of this new gene editing technique — has been a boon for scientists trying to understand the role of genes in disease. The technique for human genome modification has also raised hope for more powerful gene therapies that can delete or repair flawed genes, not just add new genes.
The first clinical trial to deploy CRISPR gene editing is now underway in China, and a U.S. trial is slated to start next year. But even though CRISPR can precisely target specific stretches of DNA, it sometimes hits other parts of the genome. Most studies that search for these off-target mutations use computer algorithms to identify areas most likely to be affected and then examine those areas for deletions and insertions.
“These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals,” says co-author of the study Alexander Bassuk, MD, PhD, professor of pediatrics at the University of Iowa.
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In the new study, the researchers sequenced the entire genome of mice that had undergone CRISPR gene editing in the team’s previous study and looked for all genetic mutations, including those that only altered a single nucleotide.
The researchers determined that CRISPR had successfully corrected a gene that causes blindness, but the labs of one of the co-authors of the study, found that the genomes of two independent gene therapy recipients had sustained mutations and deletions, none of which were predicted by computer algorithms that are used by researchers to look for off-target effects.
“Researchers who aren’t using whole genome sequencing to find off-target effects may be missing potentially important mutations,” Dr. Tsang says. “Even a single nucleotide change can have a huge impact.”
Researchers are currently working to improve the components of the CRISPR gene editing technique to increase the efficiency of editing.
However, as these most recent findings illustrate, it will be important to further examine the overall impact of the editing, regardless of how efficient it becomes.
This article has been adapted from a Columbia University Medical Center press release.