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

创造新一代转基因蚊子来控制传染病

• 批准号: 9140088
• 负责人: CRAIG MONTELL
• 金额: $ 76.75万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9140088
• 关键词: Aedes; Affect; Area; Centers for Disease Control and Prevention (U.S.); Communicable Diseases; Country; Culicidae; Dengue; Diptera; Disease; Drosophila genus; Female; Flavivirus; Generations; Genes; Health; Incidence; Indigenous; Insect Control; Insecta; Laboratories; Libido; Lyme Disease; Malaria; Modeling; Mosquito Control; Mutation; Partner in relationship; Population; Public Health; Rocky Mountain Spotted Fever; Signaling Protein; Sterility; Testing; Transgenic Organisms; United States; disorder risk; fitness; fly; gene discovery; killings; male; novel strategies; success

 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

 描述（由适用提供）：全球最具破坏性的传染病是昆虫传播疾病，疟疾和登革热。世界一半的人口生活在有这些疾病风险的地区。根据世卫组织和疾病预防控制中心的说法，去年有10亿人患有疟疾或登革热。尽管努力控制疟疾和登革热的蚊子，但它们仍然是巨大的健康问题。这些疾病影响> 100个国家，每年杀死> 100万人。登革热特别令人担忧，因为它的事件在过去50年中增加了10倍。现在，登革热病毒感染每年超过5亿人。显然，当前控制疟疾，尤其是登革热的方法是不足的。处理登革热传播的最新方法是释放带有显性突变的转基因男性蚊子，这些蚊子在交配后会导致土著雌性无菌或无法再现黄病毒。但是，这些发布策略成功的第一障碍是，转基因男性与本地男性没有充分竞争，从而极大地限制了这种原本有望的方法的可行性。我们在三种果蝇信号传导蛋白中发现了突变，这些突变大大增加了男性性驱动，这使雄性苍蝇在交配中胜过野生型雄性。由于苍蝇和蚊子都是双翅目，并且在蚊子中发现的基因是在蚊子中保守的，因此我们建议这些发现将使我们能够在蚊子中发起一种革命性的新方法，旨在增加转基因登革热蚊子的性欲。我们建议在三个相应的伊蚊基因中产生突变，我们将其定位将大大增加这些蚊子在胜任土著雄性中的适应性。作为该模型的首次测试，我们将在实验室笼子中对野生型男性进行竞争测试，然后在室外野外围墙的野外研究中进行竞争测试。我们