Rodent outbreaks have significant ecological, agricultural and economic impacts around the world. Although they can occur with increasing frequency in some parts of the world, current management practices remain ineffective. Gene drives, which are genetic elements with positively biased transmission, have been theoretically shown to eradicate large populations of invasive mice on isolated islands and could potentially serve as pre-emptive tools against mouse plagues. Using a spatially explicit individual-based model, we investigated whether a recently developed murine gene drive, tCRISPR, is effective in suppressing mouse populations within an open agricultural setting that experiences plague-like conditions with varying intensity and duration. We simulated various release strategies involving different temporal and spatial release efforts and measured the reduction in maximum plague population sizes relative to scenarios where no control was applied. Early releases allowed more time for the drive to spread before the onset of plagues, making it the most effective strategy to reduce the impact of plagues. Repeated and spatially extensive release efforts, which were initiated 3 years earlier and continued up to the onset of plagues, resulted in up to 90% reductions in the maximum population sizes compared to plagues without control. Effectiveness declined with later releases; those initiated at the onset of the plagues or later did not result in a decrease in population sizes. We tested whether the total release effort of the most effective strategy can be reduced by incorporating periods without any releases. We showed that pulsed releases with no-release gaps could be similarly effective; however, the timing of both releases was critical. Surprisingly, the lowest release effort, which was the one-time release of a single individual to the release sites, had almost no impact on the first plague, but had a substantial impact on subsequent recurring plagues that occurred 10 years later and reduced the maximum population sizes by ~80%. A newly-developed murine gene drive, tCRISPR, could be an effective pre-emptive control tool for costly mice plagues. Early releases followed by supplementation could eliminate the need to predict or closely monitor their occurrence.
