Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages

A. Simoni, R. D'Amato, C. Taxiarchi, M. Galardini, A. Trusso, R. Minuz, S. Gilli, A. Somerville, D. Shittu, A. Khalil, R. Galizi and R. Muller,  Research Square,  2023.

CRISPR-based gene drives have the potential to spread within a population and are considered as promising vector control tools. A doublesex-targeting gene drive was shown effective to suppress laboratory populations in both small and large cages, and it is considered for field application. Challenges related to the field-use of gene drives and the evolving regulatory framework demand for systems able to modulate or revert the action of gene drives, as part of post-release risk-mitigation plans. We developed an improved AcrIIA4-based anti-drive strain and showed inhibition of gene drive spread, in complex feeding and reproductive behavioural conditions. A stochastic model predicted the experimentally-observed genotypes dynamics in overlapping generations in medium- and large-sized cages and further demonstrated the effectiveness of anti-drive in different release and fitness scenarios. This study provides a further validation for the use of anti-drive system in controlling the spread of gene drive in Anopheles under complex behavioural conditions.

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