Abstract

CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages. To bridge the gap between laboratory and the field, this gene-drive technology must be challenged with vector ecology.Here we report the suppressive activity of the gene-drive in age-structured An. gambiae populations in large indoor cages that permit complex feeding and reproductive behaviours.The gene-drive element spreads rapidly through the populations, fully supresses the population within one year and without selecting for resistance to the gene drive. Approximate Bayesian computation allowed retrospective inference of life-history parameters from the large cages and a more accurate prediction of gene-drive behaviour under more ecologically-relevant settings.Generating data to bridge laboratory and field studies for invasive technologies is challenging. Our study represents a paradigm for the stepwise and sound development of vector control tools based on gene-drive.

Highlights

  • CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages

  • We recently demonstrated the success of this approach by developing a second generation gene drive, named Ag (QFS)[1], that has been used to suppress entire populations of caged mosquitoes in proof-ofprinciple experiments[9]

  • Females homozygous for the gene drive display female-male sexual development and cannot produce offspring. This strategy has proven effective for two independent gene drive designs, each tested by tracking invasion dynamics over time following single, low frequency introductions in six discretegeneration laboratory populations[9,11]

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Summary

Introduction

CRISPR-based gene-drives targeting the gene doublesex in the malaria vector Anopheles gambiae effectively suppressed the reproductive capability of mosquito populations reared in small laboratory cages. We recently demonstrated the success of this approach by developing a second generation gene drive, named Ag (QFS)[1] (previously called dsxFCRISPRh), that has been used to suppress entire populations of caged mosquitoes in proof-ofprinciple experiments[9] This gene drive is designed to target an ultra-conserved, essential sequence within the female-specific isoform of the gene doublesex, encoding a transcription factor that is the major regulator of sex determination in insects[9,10]. Females homozygous for the gene drive display female-male sexual development (intersex) and cannot produce offspring This strategy has proven effective for two independent gene drive designs, each tested by tracking invasion dynamics over time following single, low frequency introductions in six discretegeneration laboratory populations[9,11]

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