BLOCKING DENGUE TRANSMISSION BY TRANSGENIC AEDES AEGYPTI

阻断转基因埃及伊蚊传播登革热

• 批准号: 6845116
• 负责人: KENNETH E OLSON
• 金额: $ 52.41万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6845116
• 关键词: Aedes; arthropod borne communicable disease; arthropod genetics; communicable disease control; dengue; emerging infectious disease; gene induction /repression; genetic manipulation; genetic regulation; genetic transcription; genetically modified animals; southern blotting; transfection; transfection /expression vector; transposon /insertion element

DESCRIPTION: Dengue (DEN) and dengue hemorrhagic fever (DHF) have emerged as the most important mosquito-borne viral diseases affecting humans. DEN disease control is difficult because traditional vector control measures are becoming less effective and vaccines are not currently available. The molecular genetic manipulation of vector mosquitoes has been proposed as an approach to disrupt the transmission of DEN viruses and control DEN disease. The laboratory group at the Arthropod-borne and Infectious Diseases Laboratory (AIDL; Colorado State University (CSU), Fort Collins, CO) using transient alphavirus expression systems has identified gene-based, virus-specific, effector RNAs that profoundly alter the vector competence of Aedes aegypti for transmission of DEN viruses. The James laboratory (University of California, Irvine, CA) has developed methods for producing transformed mosquitoes using two different class 11 transposable elements, Hermes and mariner. Thus, for the first time, all of the components are in place to produce virus-resistant, stable lines of mosquitoes in the laboratory. Genetic analyses will be required to study gene flow of resistant-gene bearing transposons and determine if resistant genes will move through caged populations of mosquito vectors. The research program we propose has the following specific aims: 1) genetically-alter the vector mosquito, Aedes aegypti, with nonautonomous class 11 transposable elements to express anti-DEN effector genes; 2) evaluate the level of resistance and transmission-blocking potential of transgenic mosquito lines to all four serotypes of DEN viruses and among genetic variants of the viruses; and 3) evaluate the mobility and stability of anti-DEN genes as they are carried by autonomous transposable elements through cage populations of mosquitoes. Information derived in these studies may provide a new paradigm for control of vector borne diseases by interrupting the cycle of transmission at the level of the vector, which may then be directly applicable to other vector-pathogen systems.

描述：登革热 (DEN) 和登革出血热 (DHF) 已成为 影响人类的最重要的蚊媒病毒性疾病。登革热病 控制很困难，因为传统的病媒控制措施正在变得越来越困难 效果较差，目前还没有疫苗。分子遗传学 已提出操纵媒介蚊子作为破坏的一种方法 DEN 病毒的传播和控制 DEN 疾病。实验室组 节肢动物传播疾病和传染病实验室（AIDL；科罗拉多州立大学） 大学 (CSU)，柯林斯堡，科罗拉多州）使用瞬时甲病毒表达系统 已经鉴定出基于基因的、病毒特异性的效应子RNA，这些RNA可以深刻地改变 埃及伊蚊传播 DEN 病毒的载体能力。詹姆斯 实验室（加州大学欧文分校）开发了使用两种不同的 11 类转座元件 Hermes 生产转化蚊子的方法 和水手。因此，这是第一次，所有组件都就位 在实验室中培育出抗病毒、稳定的蚊子系。遗传 需要进行分析来研究抗性基因携带的基因流 转座子并确定抗性基因是否会穿过笼子 蚊媒种群。我们提出的研究计划有 以下具体目标：1）对媒介蚊子伊蚊进行基因改造 埃及伊蚊，具有非自主 11 类转座元件来表达抗 DEN 效应基因； 2) 评估电阻和传输阻塞的水平 转基因蚊子品系对所有四种 DEN 病毒血清型的潜力 病毒的遗传变异； 3）评估流动性和 抗 DEN 基因的稳定性，因为它们由自主转座子携带 通过笼子里的蚊子种群来获取元素。源自这些的信息 研究可能为控制媒介传播疾病提供新的范式 中断向量级别的传输周期，这可能 然后直接应用于其他媒介病原体系统。