BLOCKING DENGUE TRANSMISSION BY TRANSGENIC AEDES AEGYPTI

阻断转基因埃及伊蚊传播登革热

• 批准号: 6626399
• 负责人: KENNETH E OLSON
• 金额: $ 49.51万
• 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 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626399
• 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疾病。登革热 控制是困难的，因为传统的矢量控制措施正在变得 效果较差，目前还没有疫苗可用。分子遗传学 操纵媒介蚊子被认为是一种扰乱 登革热病毒的传播和登革热的控制。实验室小组 节肢动物传播和传染病实验室(AIDL；科罗拉多州 使用瞬时甲型病毒表达系统的科林斯堡大学 已经发现了基于基因的、病毒特异性的效应器RNA，这些RNA深刻地改变了 埃及伊蚊传播登革热病毒的媒介能力。《詹姆斯》 实验室(加州大学欧文分校)已经开发出使用两种不同的11类转座元件Hermes生产转化蚊子的方法 还有水手。因此，第一次，所有组件都到位，以 在实验室里生产抗病毒的稳定的蚊子品系。遗传 将需要分析来研究抗病基因生育的基因流动 转座子和确定抗性基因是否会通过笼子 蚊子媒介的种群。我们提出的研究计划具有 具体目标如下：1)对媒介蚊子伊蚊进行基因改造 埃及伊蚊，带有非自治的11类转座元件来表达抗登革热 效应基因；2)评估抗性水平和传播阻断 转基因蚊系对所有四种血清型登革热病毒和 在病毒的遗传变种中；以及3)评估移动性和 自主转座携带抗DEN基因的稳定性 通过笼子里的蚊子种群传播。从这些文件中获取的信息 研究可能为控制媒介传播的疾病提供一个新的范例 在向量级别中断传输周期，这可以 然后直接适用于其他病媒-病原体系统。