BLOCKING DENGUE TRANSMISSION BY TRANSGENIC AEDES AEGYPTI

阻断转基因埃及伊蚊传播登革热

• 批准号: 6232911
• 负责人: KENNETH E OLSON
• 金额: $ 47.9万
• 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/6232911
• 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; 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）和登革热出血热（DHF）已出现为 影响人类的最重要的蚊子传播病毒疾病。 DEN病 控制很困难，因为传统的矢量控制措施正在成为 效率较低，目前尚无疫苗。分子遗传 已经提出了对媒介蚊子的操纵作为破坏的一种方法 DEN病毒和控制DEN疾病的传播。实验室 在节肢动物传播和传染病实验室（AIDL；科罗拉多州） 大学（CSU），Collins，CO）使用瞬态α病毒表达系统 已经确定了基于基因的，病毒特异性的效应子RNA，这些效应rNA深刻改变了 埃及埃及传播DEN病毒的矢量能力。詹姆斯 实验室（加利福尼亚大学，加利福尼亚大学加利福尼亚大学）开发了使用两个不同的11级可转座元素Hermes生产转化的蚊子的方法 和水手。因此，首次将所有组件都安置在适当的位置 在实验室中产生抗病毒，稳定的蚊子线。遗传 需要分析以研究抗性基因轴承的基因流 转座子并确定抗性基因是否会通过笼 蚊子媒介的种群。我们建议的研究计划具有 以下特定目的：1）遗传驱动器蚊子，艾德斯 埃及，具有非自主类11 class class-trosposostos元素，以表达反端 效应基因； 2）评估电阻和传输障碍的水平 转基因蚊子线的潜力到DEN病毒的所有四种血清型和 在病毒的遗传变异中； 3）评估流动性和 抗Den基因的稳定性是通过自主转座携带的 通过蚊子种群的元素。这些信息中得出的信息 研究可能会为控制向量传播疾病提供新的范式 中断向量水平的传输周期，这可能 然后直接适用于其他载体 - 病原体系统。