Split drive killer-rescue: A novel threshold-dependent gene drive

A wide range of gene drive mechanisms are predicted to increase in frequency within a population even when deleterious to individuals carrying them. This should also allow associated desirable genetic material to increase in frequency. Gene drives have garnered much attention for their potential use against a range of globally important problems including disease vectors, crop pests and invasive species. Here we propose a novel gene drive mechanism that could be engineered using a combination of toxin-antidote and CRISPR components, each of which are already being developed for other gene drive designs. Population genetics mathematical models are developed here and used to demonstrate the threshold-dependent nature of the proposed system alongside its robustness to a wide range of performance parameters, each of which are of practical significance given that real-world components are inevitably imperfect. We show that although a mechanism known to cause resistance may cause the system to break down, under certain conditions, it should persist over time scales relevant for genetic control programs. This work proposes a promising new class of gene drive (with several highly desirable characteristics) that may be engineered by combining components already widely in development.