Generating sterile Anopheles mosquitoes to combat malaria transmission

Generating sterile Anopheles mosquitoes to combat malaria transmission

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Xu, X. and Champer, J.,  Research Communities by Springer Nature,  2025.

Malaria remains a deadly disease, claiming hundreds of thousands of lives worldwide every year. The primary vectors of malaria are Anopheles mosquitoes, including Anopheles gambiae and Anopheles stephensi. Controlling mosquito populations is crucial for stopping malaria transmission. Gene drive technology represents a promising alternative to traditional chemical-based control methods, offering a species-specific and eco-friendly approach. However, key challenges in developing gene drives include resistance formation due to end-joining repair after Cas9/gRNA cleavage and the fitness costs associated with drive heterozygotes.

One of the most successful gene drive designs to date targets the doublesex (dsx) gene in Anopheles gambiae, as reported by Kyrou et al. (2018). The dsx gene plays a crucial role in sex differentiation, with distinct isoforms expressed in males and females. Disrupting the female-specific isoform results in female sterility. Ideally, only homozygous females exhibit sterility due to a male-like intersex phenotype, while male homozygous and heterozygous mosquitoes of both sexes remain fertile. This makes it a suitable target for a suppression gene drive aimed at reducing the number of fertile females and ultimately eliminating the population.