The treatment of debilitating inherited disorders is one of the greatest challenges contemporary medicine faces, according to a new study. Despite the renewed optimism that CRISPR technology and improvements in genetic studies have given patients as well as their relatives in the last decade, there are still substantial concerns about the safety of these revolutionary treatments.
Published in Science Advances, the results of the study were made public recently. Scientists at the University of California, San Diego (UCSD) have developed a new, safer approach for correcting genetic faults, including postdoctoral researcher Sitara Roy, specialist Annabel Guichard, and professor Ethan Bier. There are several genetic abnormalities that might potentially be treated with this strategy since it makes use of a body’s inherent DNA repair processes.
According to Guichard:
The healthy variant can be used by the cell’s repair machinery to correct the defective mutation after cutting the mutant DNA. Remarkably, this can be achieved even more efficiently by a simple harmless nick.
The research
This “homologous chromosome-templated repair,” or HTR, may be seen in fruit flies via the synthesis of colors in their eyes. In the beginning, these mutants had eyes that were completely white. Even though CRISPR components were produced in the same flies, they showed big red patches over their eyes, indicating that the DNA repair machinery had successfully reverted the mutation. Their novel approach was tested using Cas9 variations known as “nickases” that targeted only one strand of DNA rather than both.
To their surprise, the researchers discovered that nicks in the red-eye pigmentation of mutant flies also resulted in a high amount of red-eye color restoration. Nickase repair rates of 50-70 percent compared to Cas9’s 20-30 percent, which also causes frequent mutations and targets other regions of the genome.
Precision-editing using “allelic-drives” expands the group’s past breakthroughs in precision-editing with “guide RNAs” that lead the CRISPR system to cut and replace undesirable versions of a gene with a preferred gene version.
