Maternal-effect selfish element as gene drive for Anopheles mosquitoes

按蚊是疟疾的主要媒介，疟疾是最致命和最昂贵的疾病之一 人类历史上最大的疾病。控制疟疾的措施正在变得不那么有效，因为杀虫剂和 抗药性也在增加。显然，迫切需要新的方法。一项新战略，以 控制蚊媒疾病提议引入所谓的效应基因或难治基因 进入蚊子，这将使蚊子不能有效地传播病原体。开发 在自然种群中驱动效应器基因的方法是当务之急。这样做的长期目标是 研究是开发一种高效和安全的基因驱动机制，使遗传策略能够 控制蚊媒传染病。最近，陈和他的同事(2007)报告了 在果蝇中创造了一种名为美狄亚的合成遗传元件，成功地推动了种群的增长 在实验室进行更换。果蝇的美狄亚成分由两部分组成，母体的 以人工microRNAs的形式表达毒素，抑制MyD88，MyD88是早期 胚胎发育，以及一种合子解毒剂MyD88变体的形式，该变体缺乏 因此，microRNA靶标对毒素不敏感。在我们初步结果的基础上，我们将测试 假设可以在斯氏按蚊中开发出合成的Medea基因驱动系统。我们 将1)确定在卵子发生和早期胚胎发生过程中的转录组图谱。 Stephensi；2)选择和测试AN的组件。Stephensi Medea；3)构建完整 一种。Stephensi Medea元素及其母性自私特征和基因检测 驾驶能力。

Anopheline mosquitoes are the primary vectors of malaria, one of the deadliest and most costly diseases in human history. Measures to control malaria are becoming less effective as both insecticide- and drug-resistance increases. It is clear that new approaches are urgently needed. A new strategy to control mosquito-borne diseases proposes to introduce so-called effector genes or refractory genes into the mosquito that will render the mosquitoes ineffective vectors for pathogens. Developing the means to drive effector genes in natural populations is an urgent priority. The long term objective of this study is to develop an efficient and safe gene drive mechanism that will enable genetic strategies for the control of mosquito-borne infectious diseases. Recently, Chen and colleagues (2007) reported the creation of a synthetic genetic element called Medea in Drosophila that successfully drove population replacement in laboratory. The Drosophila Medea element consists of two parts, a maternally expressed toxin in the form of artificial microRNAs that suppress Myd88, an essential gene for early embryonic development, and a zygotic antidote in the form of a variant of Myd88 that lacks the microRNA targets thus insensitive to the toxin. Building on our preliminary results, we will test the hypothesis that a synthetic Medea gene drive system can be developed in Anopheles stephensi. We will 1) determine the transcriptome profiles during oogenesis and early embryogenesis in An. stephensi; 2) select and test components of An. stephensi Medea; and 3) construct a complete An. stephensi Medea element and test for its maternal-effect selfish characteristics and gene drive ability.