CRISPR-based gene drives are self-sustaining genetic elements that have been recently generated in 22 the laboratory with the aim to develop potent genetic vector control measures targeting disease 23 vectors including Anopheles gambiae. We have shown that a gene drive directed against the gene 24 doublesex (dsx) effectively suppressed the reproductive capability of mosquito populations reared in 25 small laboratory cages. These experiments, though informative, do not recapitulate the complexity of 26 mosquito behaviour in natural environments. Additional information is needed to bridge the gap 27 between laboratory and the field to validate the vector control potential of the technology. 28

We have investigated the suppressing activity of dsx gene drive strain Ag (QFS) 1 on age-structured 29 populations of Anopheles gambiae in large indoor cages that provide a more challenging ecology by 30 more closely mimicking natural conditions and stimulating complex mosquito behaviours. Under 31 these conditions, the Ag (QFS) 1 drive spreads rapidly from a single release to the indoor large-cage 32 populations at low initial frequency, leading to full population suppression within one year and 33 without inducing resistance to the gene drive. 34