TY - JOUR T1 - Confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit <em>Aedes aegypti</em> populations JF - bioRxiv DO - 10.1101/607267 SP - 607267 AU - Héctor M. Sánchez C. AU - Jared B. Bennett AU - Sean L. Wu AU - Gordana Rašić AU - Omar S. Akbari AU - John M. Marshall Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/04/12/607267.abstract N2 - The discovery of CRISPR-based gene editing and its application to homing-based gene drive systems has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. Gene drive systems that display threshold-dependent behavior could potentially be used during the trial phase of this technology, or when localized control is otherwise desired, as simple models predict them to: a) effectively spread into partially isolated populations in a confineable manner, and b) be reversible through releases of wild-type organisms. Here, we model hypothetical releases of two recently-engineered threshold-dependent gene drive systems - reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UDMEL - to explore their ability to be confined and remediated. We simulate releases of Aedes aegypti, the mosquito vector of dengue, Zika and other arboviruses, in Yorkeys Knob, a suburb of Cairns, Australia, where previous biological control interventions have been undertaken on this species. We monitor spread to the neighboring suburb of Trinity Park, to assess confinement. Our results suggest that translocations could be introduced on a suburban scale, and remediated through releases of non-disease-transmitting male mosquitoes with release sizes on the scale of what has been previously implemented. UDMEL requires fewer releases to introduce, but more releases to remediate, including of females capable of disease transmission. Both systems are expected to be confineable to the release site; however, spillover of translocations into neighboring populations is less likely. ER -