Small Study Finds Fatal Flaw In Gene Editing Tool CRISPR
Hailed as the breakthrough of 2015 by Science magazine, the CRISPR-Cas9 gene editing tool is already being tested in clinical trials as researchers hope to harness the technology's immense potential in treating genetic diseases.
Chinese researchers are currently conducting the world's first CRISPR human trial, focused specifically on cancer patients. At the same time, a U.S. clinical trial is in the cards for next year.
Yet the CRISPR technique still remains controversial. Although many genetic researchers advocate its numerous advantages in treating a large number of diseases, from infertility to Huntington's to hemophilia, other scientists express their concerns this ground-breaking medical technology could be abused.
Now, a new study cautions the scientific community that tampering with the DNA can give rise to hundreds of unexpected consequences, causing genetic mutations that scientists cannot predict.
Unwanted CRISPR Genetic Mutations
The CRISPR-Cas9 technique alters parts of the genome, by removing, adding, or even changing sections of the DNA sequence. In view of this, the CRISPR technology could pave the way for more powerful gene therapies that not only expand the genome, but also delete or repair flawed genes.
However, despite the fact that CRISPR can target specific stretches of DNA with accurate precision, the technique can sometimes alter unwanted parts of the genome, uncovered scientists at Columbia University Medical Center or CUMC.
The researchers warn the CRISPR gene editing tool can cause the genome to undergo hundreds of unintended mutations, "including single nucleotide mutations and mutations in non-coding regions of the genome."
"We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR," says study co-author Stephen Tsang, M.D., an associate professor of pathology and cell biology at CUMC's Institute of Genomic Medicine.
Last year, his team investigated the potential of CRISPR gene editing in treating mice suffering from a type of inheritable blindness called retinitis pigmentosa.
Their more recent study, published May 30 in the journal Nature Methods, reexamined the mice's genome in an attempt to identify all the occurred mutations, including those that only altered a single nucleotide.
Looking For Errors: First Complete Sequencing Of The Entire Genome
In the past, studies have relied on computer algorithms to pinpoint the genome areas most susceptible to off-target mutations.
But now the researchers have managed to sequence the mice's entire genome to look for unpredicted mutations, such as deleted or inserted genes.
According to Alexander Bassuk, the study's other co-author and a professor of pediatrics at the University of Iowa, these algorithms were proved successful in predicting off-target mutations when scientists performed CRISPR in cells or tissues in a petri dish.
Yet, until now, no one has attempted whole genome sequencing to look for all off-target effects in living animals, Bassuk explained.
The new analysis revealed that, while CRISPR did correct the gene responsible for the onset of blindness in mice, it also produced DNA mutations in two of the test subjects, which the computer algorithms weren't able to predict.
The team discovered the two mice "sustained more than 1,500 single-nucleotide mutations and more than 100 larger deletions and insertions," shows a CUMC news release.
"Researchers who aren't using whole genome sequencing to find off-target effects may be missing potentially important mutations," emphasized Tsang, adding that "even a single nucleotide change can have a huge impact."
The scientists point out that every new therapy comes with its set of potential side effects, which is why being wary of what they are is an important step in devising safer, more accurate gene editing techniques.