Designing gene drives to limit spillover to non-target populations

Abstract

AbstractThe prospect of utilizing CRISPR-based gene-drive technology for controlling populations, such as invasive and disease-vector species, has generated much excitement. However, the potential for spillovers of gene drive alleles from the target population to non-target populations — events that may be ecologically catastrophic — has raised concerns. Here, using two-population mathematical models, we investigate the possibility of limiting spillovers and impact on non-target populations by designing differential-targeting gene drives, in which the expected equilibrium gene drive allele frequencies are high in the target population but low in the non-target population. We find that achieving differential targeting is possible with certain configurations of gene drive parameters. Most of these configurations ensure differential targeting only under relatively low migration rates between target and non-target populations. Under high migration, differential targeting is possible only in a narrow region of the parameter space. When migration is increased, differential-targeting states can sharply transition to states of global fixation or global loss of the gene drive. Because fixation of the gene drive in the non-target population could severely disrupt ecosystems, we outline possible ways to avoid this outcome. Our results emphasize that, although gene drive technology is promising, understanding the potential consequences for populations other than the targets requires detailed analysis of gene-drive spillovers, and that ways to limit the unintended effects of gene drives to non-target populations should be explored prior to the application of gene drives in natural settings.