Confinement considerations for CRISPR toxin-antidote gene drive systems

Gene drives are potentially powerful tools, able to spread throughout target populations. They could be used to modify or suppress disease vectors, invasive species, and agricultural pests. Yet, in many scenarios, confinement of the drive to only a target population is required. Several types of drives are capable of this, among the most promising of which are CRISPR toxin-antidote drives. Though showing good performance in simple models, such drives have not been thoroughly assessed in spatially structured populations. Here we evaluate three modification drive variants with varying levels of confinement. We find that Toxin-Antidote Recessive Embryo (TARE) drive and 2-locus TARE drives can usually spread in connected populations or from a single sufficiently large release. However, they can still be stopped by a migration corridor or by a sufficiently high population density gradient. 1-locus 2-drive TARE, on the other hand, will not be able to spread outside of release areas and indeed will often retreat in the face of wild-type alleles. When these drives arrive at a point source such as a port, only the standard TARE drive has a significant chance of establishing if releases occur at sufficiently high frequency and quantity. However, in models with parental care among a limited number of offspring, TARE drives become more invasive, with lower introduction thresholds. Overall, we find that spatial and other ecological factors can substantially affect the outcome of a confined CRISPR toxin-antidote drive release.