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Abstract

CRISPR/Cas9-based technologies have revitalized interest in gene-editing technologies as means to control mosquito-borne diseases. Amongst candidate disease-control mechanisms, gene- replacement strategies are considered some of the most promising due to their resilience to generation of resistant alleles (caused by errors in homology-directed repair). These approaches focus on releasing and introgressing genes that prevent mosquitoes from transmitting pathogens to humans, thus disrupting the transmission chain.Genetically isolated populations provide perfect testing grounds to assess the viability of genetic-modification constructs, as they limit the probability of the drive escaping the area of study whilst also restricting the impact of heterogeneity in variables such as migration and spatial structure. The islands of São Tomé and Príncipe, in the equatorial region west of the African mainland are a couple of such settings that are being considered as potential testing grounds for gene drive studies.In this work, we explore release strategies to introgress a transgenic construct in a mosquito population using our published gene-drive model: MGDrivE. In doing so, we find that even though there is a benefit in increasing the ratio of the releases of transgenic mosquitoes (with respect to the natural population), a limit exists above which performing more releases does not significantly increase the speed at which the transgene takes over the population. Additionally, we find that changes in the genetic standing variation do not affect the time to introgression; and that, even though sex of the released mosquitoes (mixed, gravid, or male-only) does impact the extent of the effects, their viability has to be assessed with respect to the necessary mosquito sex-sorting labour.
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