Engineering drive-selection balance for localised population suppression with neutral dynamics

Abstract

Whilst the release of sterile males has been highly successful in suppressing some pest populations, it is impractical for other species due to the males disappearing after a single generation, necessitating large, repeated releases to maintain sufficient impact. Synthetic gene drives promise more efficient approaches since they can increase in frequency from rare, yet this also allows them to spread across a landscape, which may not always be desired. Between these two extremes are selectively neutral genetic constructs which persist at the frequency they are released, offering the potential for efficient suppression that remains localised. One way to achieve this would be to have perfect balance, at all construct frequencies, between gene drive increasing frequency and selection decreasing it. Here we describe a way to create this balance involving a toxin-antidote genetic construct that causes recessive lethality, encodes a genomic editor that makes dominant lethal edits in the genome, and provides protection against the action or consequences of the editing. Computer modelling shows that this design can be 100-fold more efficient than sterile males, increasing to 1000-fold more when released alongside a genetic booster. We describe designs for CRISPR-based molecular construction, including options that avoid using recoded genes as antidotes.