Components of the Medea gene drive system in a mosquito Aedes aegypti

埃及伊蚊的 Medea 基因驱动系统的组成部分

• 批准号: BB/S001964/1
• 负责人: Jaroslaw Krzywinski
• 金额: $ 96.6万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS001964%2F1
• 关键词: Components; Medea; gene; drive; system

Mosquito-borne viral diseases, such as dengue, chikungunya, yellow fever, and Zika continue to be a major international public health problem. Despite control efforts, the numbers of infections are on the increase, which indicates that the existing control strategies, relying on suppression of mosquito vector populations, are not effective. The mosquito Aedes aegypti, responsible for the great majority of infections with these viruses, is difficult to control with the conventional tools. It breeds in various, often cryptic, man-made containers, and their females bite during the day, making their targeting with insecticides very challenging. Moreover, increasing resistance to insecticides in the Ae. aegypti populations further exacerbates the situation. To reduce disease burden, new genetic control strategies have been proposed, aiming at suppression of mosquito populations or at mosquito population modification by releasing engineered mosquitoes incapable of virus transmission. The latter strategies, to be effective, require a mechanism that would allow a rapid spread of the anti-pathogen synthetic constructs through the entire mosquito populations. A gene drive mechanism, called Medea, constructed thus far only in a fruit fly Drosophila melanogaster, has been demonstrated to possess the required invasive properties. Efforts to develop functional Medea element in mosquitoes have not yet met with success, because information about the relevant aspects of mosquito developmental biology is still lacking. In this study, we will focus on elucidation of the key developmental processes occurring in ovaries during egg production and in early Ae. aegypti embryos to identify the most optimal genetic constituents of the Medea element functional in this mosquito species. The identified sequences will be individually validated in transgenic mosquito lines and, subsequently used for the creation of a proof-of-principle functional Medea gene drive in Aedes.

蚊媒病毒性疾病，如登革热、基孔肯雅热、黄热病和寨卡病毒，仍然是一个主要的国际公共卫生问题。尽管作出了控制努力，但感染人数仍在增加，这表明现有的依赖于抑制蚊媒种群的控制战略是无效的。埃及伊蚊是感染这些病毒的绝大多数人的罪魁祸首，用传统工具很难控制它。它在各种通常神秘的人造容器中繁殖，它们的雌性在白天叮咬，这使得它们以杀虫剂为目标非常具有挑战性。此外，增加了对杀虫剂的抗性。埃及人的数量进一步加剧了这种情况。为了减少疾病负担，人们提出了新的基因控制策略，旨在通过释放不能传播病毒的工程蚊子来抑制蚊子种群或改变蚊子种群。后一种策略要有效，需要一种机制，允许抗病原体合成结构在整个蚊子种群中迅速传播。到目前为止，一种名为Medea的基因驱动机制仅在果蝇黑腹果蝇中构建，已被证明具有所需的侵袭特性。在蚊子中开发有功能的美狄亚成分的努力尚未取得成功，因为关于蚊子发育生物学的相关方面的信息仍然缺乏。在这项研究中，我们将重点阐明在卵子生产期间和Ae早期卵巢中发生的关键发育过程。埃及伊蚊胚胎，以确定在该蚊子物种中发挥功能的Medea元件的最优遗传成分。识别出的序列将在转基因蚊子株系中单独验证，并随后用于在伊蚊中创建原理证明功能的Medea基因驱动。