Experimental Evaluation of Transgenic Anopheles gambiae Strains Carrying Gene Drive Constructs for Malaria Transmission Suppression in Nigerian Vector Populations

CRISPR-based gene drive systems targeting Anopheles gambiae reproductive fitness offer a potentially transformative population suppression approach for malaria vector control, but their efficacy and ecological safety must be evaluated in African genetic backgrounds before deployment considerations. This doctoral study experimentally evaluated two transgenic An. gambiae strains carrying doublesex gene drive constructs (designated AgDSX-NG1 and AgDSX-NG2) in simulated Nigerian vector population contexts. Wild-type An. gambiae specimens collected from Southwest and Northwest Nigeria were colonised, and cage trials assessed drive inheritance rates, female sterility penetrance, population suppression kinetics, and fitness costs under varying temperature and humidity conditions. Drive inheritance in heterozygous females was 94.3 percent for AgDSX-NG1, confirming super-Mendelian transmission. Female sterility penetrance reached 98.7 percent. Cage population suppression to undetectable levels was achieved within nine generations in small-cage trials with equal drive-to-wild-type introduction ratios. Fitness cost analysis identified a 12.4 percent reduced male competitive mating success relative to wild-type in mixed-population cages. Fitness costs did not prevent population suppression. Cross-reactivity modelling with Nigerian Anopheles arabiensis populations predicted minimal drive spillover risk based on sequence divergence at target sites. These data provide foundational Nigerian-context efficacy and safety evidence to inform regulatory and ethical deliberations on contained field evaluation of gene drive constructs. Keywords: gene drive, Anopheles gambiae, doublesex, population suppression, malaria vector control.