Bayesian network-based risk assessment of synthetic biology: Simulating CRISPR-Cas9 gene drive dynamics in invasive...

Gene drive technology has been proposed to control invasive rodent populations as an alternative to rodenticides. However, this approach has not undergone risk assessment that meets criteria established by Gene Drives on the Horizon, a 2016 report by the National Academies of Sciences, Engineering, and Medicine. To conduct a risk assessment of gene drives, we employed the Bayesian network-relative risk model to calculate the risk of mouse eradication on Southeast Farallon Island using a CRISPR-Cas9 homing gene drive construct. We modified and implemented the R-based model "MGDrivE" to simulate and compare 60 management strategies for gene drive rodent management. These scenarios spanned four gene drive mouse release schemes, three gene drive homing rates, three levels of supplemental rodenticide dose, and two timings of rodenticide application relative to gene drive release. Simulation results showed that applying a supplemental rodenticide simultaneously with gene drive mouse deployment resulted in faster eradication of the island mouse population. Gene drive homing rate had the highest influence on the overall probability of successful eradication, as increased gene drive accuracy reduces the likelihood of mice developing resistance to the CRISPR-Cas9 homing mechanism.