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

Rocco D’Amato, Chrysanthi Taxiarchi, Marco Galardini, Alessandro Trusso, Roxana L. Minuz, Silvia Grilli, Alastair G. T. Somerville, Dammy Shittu, Ahmad S. Khalil, Roberto Galizi, Andrea Crisanti, Alekos Simoni () and Ruth Müller ()
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Rocco D’Amato: Genetics and Biology (Polo GGB)
Chrysanthi Taxiarchi: Imperial College London
Marco Galardini: Boston University
Alessandro Trusso: Genetics and Biology (Polo GGB)
Roxana L. Minuz: Genetics and Biology (Polo GGB)
Silvia Grilli: Imperial College London
Alastair G. T. Somerville: Imperial College London
Dammy Shittu: Imperial College London
Ahmad S. Khalil: Boston University
Roberto Galizi: Keele University
Andrea Crisanti: Imperial College London
Alekos Simoni: Genetics and Biology (Polo GGB)
Ruth Müller: Genetics and Biology (Polo GGB)

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract CRISPR-based gene drives have the potential to spread within populations and are considered as promising vector control tools. A doublesex-targeting gene drive was able to suppress laboratory Anopheles mosquito populations in 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 suggest that systems able to modulate or revert the action of gene drives, could be part of post-release risk-mitigation plans. In this study, we challenge an AcrIIA4-based anti-drive to inhibit gene drive spread in age-structured Anopheles gambiae population under complex feeding and behavioural conditions. A stochastic model predicts the experimentally-observed genotype dynamics in age-structured populations in medium-sized cages and highlights the necessity of large-sized cage trials. These experiments and experimental-modelling framework demonstrate the effectiveness of the anti-drive in different scenarios, providing further corroboration for its use in controlling the spread of gene drive in Anopheles.

Date: 2024
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DOI: 10.1038/s41467-024-44907-x

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