New Genetic Systems to Neutralize Gene Drives

While gene drives carry the power to immunize mosquitoes against malarial parasites, concerns have been raised regarding the safety of releasing such systems into wild populations. Now, scientists at the University of California San Diego have developed two new active genetic systems that address such risks by halting or eliminating gene drives in the wild. Their findings were published on Molecular Cell. 

The team studied fruit flies and looked for ways to mitigate the risks of gene drives. "One way to mitigate the perceived risks of gene drives is to develop approaches to halt their spread or to delete them if necessary," said senior author Ethan Bier. "There's been a lot of concern that there are so many unknowns associated with gene drives. Now we have saturated the possibilities, both at the genetic and molecular levels, and developed mitigating elements."

The first neutralizing system, called e-CHACR (erasing constructs hitchhiking on the autocatalytic chain reaction) is designed to halt the spread of a gene drive by "shooting it with its own gun." e-CHACRs use the CRISPR enzyme Cas9 carried on a gene drive to copy itself, while simultaneously mutating and inactivating the Cas9 gene. Xu says an e-CHAKRA can be placed anywhere in the genome.

The second neutralizing system, called ERACR (element reversing the autocatalytic chain reaction), is designed to eliminate the gene drive altogether. ERACRs are designed to be inserted at the site of the gene drive, where they use the Cas9 from the gene drive to attack either side of the Cas9, cutting it out. Once the gene drive is deleted, the ERACR copies itself and replaces the gene-drive.

"Because ERACRs and e-CHACRs do not possess their own source of Cas9, they will only spread as far as the gene drive itself and will not edit the wild type population," said co-author Emily Bulger. "These technologies are not perfect, but we now have a much more comprehensive understanding of why and how unintended outcomes influence their function and we believe they have the potential to be powerful gene drive control mechanisms should the need arise."