Creation of a new generation of transgenic mosquitoes to control infectious disease



 DESCRIPTION (provided by applicant): The most devastating infectious diseases worldwide are the insect-borne diseases, malaria and Dengue fever. Half the world's population lives in areas at risk for these diseases. According to WHO and the CDC, one billion people came down with malaria or Dengue last year. Despite intensive efforts to control the mosquitoes that spread malaria and Dengue, they remain enormous health problems. These diseases affect >100 countries, and kill >1,000,000 people each year. Dengue is of particular concern, as its incidence has increased 10-fold over the last 50 years. Now, the Dengue flavivirus infects upwards of 500,000,000 people annually. Clearly, current approaches to control malaria and, especially Dengue, have been inadequate. The latest approach to dealing with the spread of Dengue, is to release transgenic male mosquitoes bearing dominant mutations that, upon mating, render indigenous females either sterile or unable to reproduce the flavivirus. However, the #1 obstacle to the success of these release strategies is that the transgenic males do not compete adequately with native males, greatly limiting the feasibility of this otherwise promising approach. We discovered mutations in three Drosophila signaling proteins that greatly increase male sex drive, and this allows the male flies to outcompete wild-type males in mating. Since flies and mosquitoes are both Diptera, and the genes we discovered in flies are conserved in mosquitoes, we propose that these findings will allow us to launch a revolutionary new approach in mosquitoes, aimed at increasing the sex drive of transgenic Dengue mosquitoes-Aedes aeypti. We propose to create mutations in the three corresponding Aedes genes, which we posit will greatly increase the fitness of these mosquitoes in outcompeting indigenous males. As a first test of this model, we will perform competition tests with wild-type males in laboratory cages, and then in field cage studies in outdoor field enclosures. We