![]() Promising strains are then tested to determine if the gene drive can spread in small caged populations, and to compare invasion dynamics with prediction. Typically, the development of candidate gene drive strains for potential vector control involves assessment of basic parameters concerning both fitness and drive, such as the homing rate, life-span and fecundity, however these parameters are notoriously difficult to estimate and often context-specific. 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 discrete-generation laboratory populations 9, 11. Females homozygous for the gene drive display female-male sexual development (intersex) and cannot produce offspring. 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. We recently demonstrated the success of this approach by developing a second generation gene drive, herein named Ag(QFS)1 (previously called dsxF CRISPRh), that has been used to suppress entire populations of caged mosquitoes in proof-of-principle experiments 9. One strategy to mitigate against the likelihood of target-site resistance arising is to target sequences that show high levels of functional constraint and can therefore not easily tolerate variant alleles 1. To this end, we and others have adopted a step-wise approach to the development and testing of gene drives in progressively rigorous and challenging conditions 4.įirst generation suppression drives failed to maintain their spread when tested in small, caged-population experiments within an Arthropod Containment Level 2 laboratory because of the creation and selection of drive-resistant alleles, sometimes exacerbated by unintended fitness costs in ‘carrier’ individuals 5, 6, 7, 8. To be effective for the control of malaria in sub-Saharan Africa, such a strain must be able to compete effectively with wild populations of Anopheles gambiae, and remain effective over the medium to long-term. One potentially powerful strategy aims to reduce the total number of mosquitoes by spreading a mutation that blocks female reproduction 3. First proposed in 2003, these elements use a mechanism of cut and paste (homing) in the germline to facilitate their autonomous spread from a very low initial release frequency 1, 2. Our study represents a paradigm for the stepwise and sound development of vector control tools based on gene-drive.ĬRISPR-based gene drives are selfish genetic elements that can be used to modify entire populations of the malaria mosquito for sustainable vector control. ![]() Generating data to bridge laboratory and field studies for invasive technologies is challenging. 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. 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. gambiae populations in large indoor cages that permit complex feeding and reproductive behaviours. Here we report the suppressive activity of the gene-drive in age-structured An. To bridge the gap between laboratory and the field, this gene-drive technology must be challenged with vector ecology. 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.
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