For an article in New Scientist, Carissa Wong describes a 'softer' version of the CRISPR gene editing approach. The strategy involves single-stranded DNA breaks introduced by "nickase" versions of the Cas9 enzyme rather than the double-strand breaks typically associated with Cas9 activity, she explains, while using one copy of a chromosome as a reference for repairing the other, mutation-carrying copy of the chromosome.
The "homologous chromosome-templated repair" strategy is being touted as a more efficient approach to gene editing, and was reported in Science Advances late last week. There, a University of California at San Diego-led research team used the nickase enzyme to correct an eye color mutation in Drosophila fruit flies.
Using Cas9-derived nickases dubbed D10A and H840A, the researchers successfully edited some 40 percent to 65 percent of the cells targeted with the approach — up from the 20 percent to 30 percent gene editing success the investigators achieved with traditional CRISPR-Cas9 gene editing on the somatic fly cells.
"The team didn't introduce any extra pieces of DNA as a template for the cell to correct the mutation on the chromosome," Wong notes, "so the molecular machinery must have used the other chromosome — inherited from the other parent — as a template. The team was able to confirm this was the case."