BLOCKING DENGUE TRANSMISSION BY TRANSGENIC AEDES AEGYPTI

阻断转基因埃及伊蚊传播登革热

• 批准号: 6488776
• 负责人: KENNETH E OLSON
• 金额: $ 48.12万
• 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/6488776
• 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）已经出现， 影响人类的最重要的蚊媒病毒性疾病。DEN病 控制是困难的，因为传统的矢量控制措施正在成为 效果较差，目前还没有疫苗。分子遗传 已经提出操纵病媒蚊子作为破坏 登革病毒的传播和控制登革病毒病。实验室组 节肢动物传播和传染病实验室（AIDL;科罗拉多州 University（CSU），柯林斯堡，CO）使用瞬时甲病毒表达系统 已经确定了基于基因的，病毒特异性的，效应RNA，深刻地改变了 埃及伊蚊传播登革病毒的能力。詹姆斯 一个实验室（加州大学，Irvine，CA）已经开发了使用两种不同的11类转座因子爱马仕产生转化蚊子的方法 水手因此，第一次，所有的组成部分都到位， 在实验室里培育出抗病毒的稳定蚊子品系。遗传 需要进行分析以研究抗性基因携带的基因流 转座子，并确定是否抗性基因将通过笼 蚊子传播媒介的数量。我们提出的研究计划， 以下具体目标：1）遗传改变媒介蚊子，伊蚊 埃及，具有非自主的11类转座因子以表达抗DEN 效应基因; 2）评估抗性和传播阻断水平 转基因蚊子品系对所有四种血清型DEN病毒的潜力， 在病毒的遗传变异中;和3）评估移动性， 抗登革病毒基因的稳定性，因为它们是由自主转座 通过蚊子的笼子种群的元素。信息来源于这些 这些研究可能为控制病媒传播疾病提供一种新的范例， 在病媒水平上中断传播周期， 然后直接应用于其他媒介-病原体系统。