Engineering the genetics of wild mosquito populations to fight infectious disease

对野生蚊子种群进行基因改造以对抗传染病

• 批准号: 8306138
• 负责人: BRUCE A HAY
• 金额: $ 79.45万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306138
• 关键词: Area; Automobile Driving; Collaborations; Communicable Diseases; Communities; Coupled; Culicidae; Dengue; Disease; Elements; Environment; Frequencies; Genes; Genetic; Genetic Engineering; Goals; Insecticides; Link; Malaria; Modification; Pharmaceutical Preparations; Population; Population Replacements; Staging; Technology; Transgenes; Work; cost; disorder prevention; fighting; fitness; genetic element; human disease; killings; pathogen; social; vector; vector mosquito

Mosquitoes are essential vectors for major human diseases such as malaria and dengue fever, which together infect hundreds of millions each year, killing millions. Current approaches to disease prevention, which include anti-pathogen drugs and vector suppression through the use of insecticides or environment modification, are insufficient. Replacement of wild mosquito populations with genetically modified counterparts that cannot transmit disease provides an alternative approach to disease prevention. However, mosquitoes carrying genes for disease refractoriness are not expected to have a higher fitness than native mosquitoes, and wild populations are large, dispersed over wide areas, and partially reproductively isolated. Thus, effective population replacement requires that genes conferring disease refractoriness be coupled with a genetic mechanism for driving these genes through the wild population at greater than Mendelian frequencies. We have developed a synthetic selfish genetic element (Medea) that can spread rapidly through a population, even if its presence or that of a linked cargo results in a fitness cost. Medea is the only selfish genetic element that has multiple features required for scientific and social acceptance of transgene release into the wild: the selfish genetic element and its cargo remain tightly linked; possibilities for horizontal spread within other species are limited; transgene recall from the wild and/or cycles of population replacement can be carried out. We will develop Medea and related drive mechanisms for several important mosquito vector species. This work will be carried out in collaboration with others who have developed transgenes conferring disease refractoriness and/or who can carry out cage trials to study selfish element/effector spread and efficacy in populations of uninfected and infected mosquitoes. My goal is to bring population replacement technology to the stage where it can be applied successfully, and the communities involved will have enough confidence the technology can be controlled to allow its use.

蚊子是主要人类疾病（例如疟疾和登革热）的重要媒介 发烧，每年共同感染数亿人，造成数百万。当前的 预防疾病的方法，其中包括抗病原药和抑制媒介 通过使用杀虫剂或环境修饰，不足。 用基因改良的对应物代替野生蚊子种群 传播疾病为预防疾病提供了另一种方法。然而， 携带疾病耐火基因的蚊子预计不会具有较高的 健身比本地蚊子和野生种群大，分散在广阔的地区， 并部分生殖分离。因此，有效的人口更换要求 赋予疾病易碎性的基因与驱动的遗传机制结合 这些基因通过野生群体大于门德尔频率。 我们已经开发了一种合成的自私遗传元素（MEDEA），可以迅速传播 通过人口，即使其存在或连接的货物的存在也会带来健身成本。 Medea是唯一具有科学和具有多个特征的自私遗传元素 转基因释放到野外的社会接受：自私的遗传元素及其货物 保持紧密联系；其他物种内水平传播的可能性受到限制； 可以从野生和/或人口替代周期中进行转基因召回。 我们将开发几种重要蚊子矢量的MEDEA和相关驱动机制 物种。这项工作将与已经开发的其他人合作进行 转基因赋予疾病折磨和/或可以进行笼子试验以研究 未感染和感染的人群中的自私元素/效应子传播和功效 蚊子。我的目标是将人口替代技术带到舞台上 成功应用，所涉及的社区将具有足够的信心 可以控制技术以允许其使用。