Tethered homing gene drives: a new design for spatially restricted population replacement and suppression

Optimism regarding potential epidemiological and conservation applications of modern gene drives is tempered by concern about the possibility of unintended spread of engineered organisms beyond the target population. In response, several novel gene drive approaches have been proposed that can, under certain conditions, locally alter characteristics of a population. One challenge for these gene drives is the difficulty of achieving high levels of localized population suppression without very large releases in the face of gene flow. We present a new gene drive system, Tethered Homing (TH), with improved capacity for both localization and population suppression. The TH drive is based on driving a payload gene using a homing construct that is anchored to a spatially restricted gene drive. We use a proof-of-concept mathematical model to show the dynamics of a TH drive that uses engineered underdominance as an anchor. This system is composed of a split homing drive and a two-locus engineered ...