Development and testing of a novel Killer-Rescue self-limiting gene drive system in Drosophila melanogaster

<p>Here we report the development and testing of a novel self-limiting gene drive system, Killer-Rescue, in <i>Drosophila melanogaster</i>. This system is composed of an auto-regulated Gal4 Killer (K) and a Gal4-activated Gal80 Rescue (R). Overexpression of Gal4 is lethal, but in the presence of R activation of Gal80 leads to much lower levels of Gal4 and rescue of lethality. We demonstrate that with a single 2:1 engineered to wildtype release, K drives R through the population and after nine generations more than 98% of the population carry R and less than 2% of the population are wildtype flies. We discuss how this simple Killer-Rescue gene drive system may be readily adapted for population replacement in a human health pest, <i>Aedes aegypti</i>, or for population suppression in an agricultural pest, <i>Drosophila suzukii</i>.</p>