%0 Journal Article %1 D’Amato2024 %A D'Amato, R %A Taxiarchi, C %A Galardini, M %A Trusso, A %A Minuz, R L %A Grilli, S %A Somerville, A G T %A Shittu, D %A Khalil, A S %A Galizi, R %A Crisanti, A %A Simoni, A %A Müller, R %D 2024 %J Nat Commun %K haeussler %N 1 %P 952 %R 10.1038/s41467-024-44907-x %T Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages %U https://pubmed.ncbi.nlm.nih.gov/38296981/ %V 15 %X 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.