Gene therapy, which involves adding extra genes to cells, was first used to cure people in 1990, but it is mainly useful for treating rare genetic disorders. In contrast, gene-editing, which involves altering existing genes inside cells, promises to treat or cure a much wider range of conditions, from HIV infection to high blood cholesterol.
The CRISPR/Cas9 genome-editing technique set the molecular biology field ablaze when its game-changing potential was realized only a few short years ago.
“We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single-nucleotide mutations and mutations in noncoding regions of the genome,” explained study co-author Stephen Tsang, M.D., Ph.D., associate professor of ophthalmology, pathology and cell biology at CUMC, Columbia’s Institute of Genomic Medicine and the Institute of Human Nutrition.
Tsang and his team have conducted the first whole-genome screening of a living organism that’s undergone CRISPR gene-editing to discover that unwanted mutations can crop up in areas that are totally unrelated to the targeted genes.
“These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole-genome sequencing (WGS) has not been employed to look for all off-target effects in living animals,” noted study co-author Alexander Bassuk, M.D., Ph.D., professor of pediatrics at the University of Iowa.
The technique works like a biological ‘cut and paste’ tool, where researchers use a protein to seek out a particular gene and cut it out of the genome, replacing it with DNA of their choice, for example, they could swap a defective gene for a healthy one.
And unlike many promising medical inventions, CRISPR has continued to live up to its potential.
“This finding warns that CRISPR technology must be further tailored, particularly before it is used for human gene therapy,” the researchers wrote.
The study that was published in the journal Nature Methods.