Population seasonality and release timing significantly affect the probability of establishment for small releases of gene drive mosquitoes

Population seasonality and release timing significantly affect the probability of establishment for small releases of gene drive mosquitoes

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Nikolov, MO, A. L.; Beaghton, A. K.; Beaghton, P. J.; Wenger, E. A.; Burt, A.; Welkhoff, P. A.,  American Journal of Tropical Medicine and Hygiene,  99:367-367. 2018.

Highly efficient CRISPR/Cas9 gene-drive systems have recently been developed, targeting reproductive-capacity and malaria-competency loci of malaria transmitting vector species, such as An. gambiae. The resulting drive systems aim to either suppress the local wild-type population or alter its genome, conveying desirable phenotypes such as P. falciparum refractoriness. The potential for sustained spread of gene drive constructs as proposed for malaria and a variety of other applications (pest control, tick borne diseases, dengue) has raised concerns for unintentional or unauthorized organism release outside approved and strictly-regulated trial sites. Previous analyses posit that as few as one or two gene drive organisms carrying efficient gene drive cassettes may establish a permanent (sub)population of genetically-modified (GM) mosquitoes with probability >50%. While these results are broad and cautionary, we show that seasonality is a fundamental environmental characteristic to consider when modeling decision variables. For the first time, we investigate the impact of gene-drive release timing and numbers on the establishment probability of GM vectors in the context of realistic seasonal population variation. We model a male sex bias, driving-Y population suppression gene drive, targeting An. gambiae, since these are among the first field trials candidate constructs. We analyze gene-drive establishment in geographies of different seasonality and spatial vector population features. We show that releasing a small number of gene-drive mosquitoes over the few weeks in the beginning of the wet season facilitates population founder effects and high establishment probability: between 60% – 80% for releases of as few as one or two mosquitoes. However, releasing genedrive mosquitoes outside this time results in much lower establishment probability, typically <20%. Our findings address crucial ethical and environmental concerns, which may guide whether, how, and where to set up gene-drive trials.