Gene Editing of Olfactory Receptors to Alter Host-Seeking Behaviour in Aedes aegypti Mosquitoes
DOI::
https://doi.org/10.70102/AEJ.2026.18.1.7کلمات کلیدی:
CRISPR-Cas9, Olfactory receptors, Aedes aegypti, Host-seeking behaviour, Gene editing.چکیده
Over 700,000 deaths are annually caused by the effects of mosquito-borne diseases, Aedes aegypti being the main carrier in the case of dengue, Zika, and chikungunya. The traditional methods to control insects using insecticides have become the cause of significant environmental issues, such as ecological imbalance, non-target toxicity, and development of resistance, and thus, sustainable alternatives are required. The olfactory receptors (ORs) are also important in the mediating host-seeking behaviour in mosquitoes as they detect volatile compounds of human origin. The paper used CRISPR-Cas9 gene editing to silence the genes of two olfactory receptors, Or4 and Or8, on the Ae. aegypti Liverpool strain. The guide RNAs were selected to target conserved domains and microinjection done on 300 embryos showed a survival rate of 47% and 68% editing efficiency was established by molecular analysis through frameshift mutations. In 2022-2023, behavioural assays revealed a 73% decrease in upwind flight response to human odor (p<0.001) of edited mosquitoes. Experiments in human landing catch have shown an 81% reduction in the rate of landing relative to wild-type controls, which implies a significant reduction in the degree of interaction between humans and vectors. Electrophysiological responses indicated that there was considerable attenuation of antennal responses to important human odorants including lactic acid, 1-octen-3-ol and ammonia. Confocal microscopy also demonstrated distressed glomerular targeting in olfactory sensory neurons to the antennal lobes. Notably, no meaningful impacts on the viability of mosquitoes and fecundity were detected, which implies behavioural change does not impair ecological fitness. Environ-wise, this is a non-lethal, eco-friendly approach to controlling vectors that helps to keep the ecosystem stable though the decrease of the disease transmission and the preservation of the mosquito population. The results give a basis in designing gene drive constructs that are used to suppress behaviour and not kill the population as it aims at achieving sustainable and eco-friendly control of vectors that do not cause harm to the environment and is less dependent on chemical intervention.