Spatial confinement of gene drives: Assessing risk of failure using global sensitivity analysis

Gene drives allow pest populations to be genetically modified to reduce their harm on agriculture and human health. The genetic modification, or payload, spreads within a target population at rates exceeding normal Mendelian inheritance. While gene drives have demonstrated immense potential in laboratory populations, they present unique challenges. Foremost among these challenges is spatial confinement, or ensuring that the payload remains confined to target populations. However, there is an inherent tension between gene drive spread and spatial confinement: increasing the spreading efficiency of a gene drive increases the risk of escape, while engineering confinement mechanisms increases the risk of gene drive extinction. In this work, we explore spatial outcomes in gene drives designed for spatial confinement and the dependence of these outcomes on target organism dispersal and payload fitness cost. We use a stochastic spatial model to compute the probability of failure for each gene drive, and use techniques from global sensitivity analysis to quantify the contribution of dispersal and fitness cost to variance in gene drive performance. Our findings reveal how spatial outcomes are affected by key parameters, and how this sensitivity varies tremendously between different gene drives. These spatial properties can be used to classify gene drive behavior and are useful to determine suitability for a particular application.