Malaria control with transgenic mosquitoes

Abstract

John Marshall and Charles Taylor review recent advances in the development of transgenic mosquitoes for malaria control.

Figure 1. Mechanism for Blocking Malaria Transmission in the Mosquito

Left: Mosquitoes become infected with the malaria parasite upon taking an infected human blood-meal. This produces an oocyst in the mosquito's gut wall (light red). When the oocyst ruptures, it releases sporozoites that pass through the gut (dark red) and into the hemocoel (white). The sporozoites are then amplified and migrate through the mosquito's body to the salivary glands, ready to infect a new human. Right: The laboratory of Marcelo Jacobs-Lorena at Johns Hopkins University has identified receptor sites for proteins that are necessary for the malaria parasite to pass through the gut wall after the oocyst ruptures. The same receptors are involved with the passage of sporozoites into the salivary glands. The laboratory has produced small proteins that preferentially occupy these sites (blue), blocking transmission of sporozoites through the gut wall and into the salivary glands. The appropriate gene constructs have been introduced into An. stephensi mosquitoes, thus rendering them refractory to P. berghei (a model system for human malaria).

Figure 2. Parental Crosses Representing the Reproductive Advantage of the Medea Allele

Females carrying the Medea allele produce a maternally expressed toxin (red outer circle) that is deleterious to their offspring. Offspring who carry the Medea allele are rescued by a zygotically expressed antidote (green inner circle) expressed by the same allele. Offspring of heterozygous females who do not inherit the Medea allele are killed by the toxin because they lack the antidote (yellow represents lack of the toxin/antidote). This distorts the offspring ratio in favor of the Medea allele.