Genetic approaches to interfere with malaria transmission by vector mosquitoes

Malaria remains one of the most devastating diseases worldwide, causing over 1 million deaths every year. The most vulnerable stages of Plasmodium development in the vector mosquito occur in the midgut lumen, making the midgut a prime target for intervention. Mosquito transgenesis and paratransgenesis are two novel strategies that aim at rendering the vector incapable of sustaining Plasmodium development. Mosquito transgenesis involves direct genetic engineering of the mosquito itself for delivery of anti-Plasmodium effector molecules. Conversely, paratransgenesis involves the genetic modification of mosquito symbionts for expression of anti-pathogen effector molecules. Here we consider both genetic manipulation strategies for rendering mosquitoes refractory to Plasmodium infection, and discuss challenges for the translation of laboratory findings to field applications.

► Mosquito gut is a prime target for interfering with Plasmodium cycle in its vector.
► Genetic approaches and challenges to block malaria transmission are considered.
► Transgenic mosquitoes are engineered to produce anti-Plasmodium molecules.
► Paratransgenesis uses engineered symbionts to deliver anti-Plasmodium molecules.
► Both approaches hold promise but field implementation issues remain to be resolved.