Engineered action at a distance: blood-meal-inducible paralysis in Aedes aegypti

Background: Population suppression through mass-release of Aedes aegypti males carrying dominant-lethal transgenes has been demonstrated in the field. Where population dynamics show negative density-dependence, suppression can be enhanced if lethality occurs after the density-dependent (i.e. larval) stage. Existing molecular tools have limited current examples of such Genetic Pest Management (GPM) systems to achieving this through engineering ‘cell-autonomous effectors’ i.e. where the expressed deleterious protein is restricted to the cells in which it is expressed – usually under the control of the regulatory elements (e.g. promoter regions) used to build the system. This limits the flexibility of these technologies as regulatory regions with useful spatial, temporal or sex-specific expression patterns may only be employed if the cells they direct expression in are simultaneously sensitive to existing effectors, and also precludes the targeting of extracellular regions such as cell-sur...

背景：通过大规模释放携带显性致死转基因的埃及伊蚊雄蚊实现种群抑制的方法已在实地得到验证。当种群动态呈现负密度依赖性时，若致死效应发生在密度依赖阶段（即幼虫期）之后，抑制效果可得到增强。现有分子工具限制了此类遗传害虫治理（Genetic Pest Management, GPM）系统的现有实例，使其只能通过改造‘细胞自主效应因子（cell-autonomous effectors）’来实现这一目标——即表达的有害蛋白被限制在其表达所在的细胞内，通常受构建该系统所用的调控元件（如启动子区域）控制。这限制了这些技术的灵活性，因为只有当具有有用空间、时间或性别特异性表达模式的调控区域所指导表达的细胞同时对现有效应因子敏感时，才能使用这些调控区域；此外，这也排除了靶向细胞外区域（如cell-sur...）的可能性。