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Gene delivery for Anopheles mosquitoes

按蚊的基因传递

基本信息

批准号：
9900713
负责人：
Jason L Rasgon
金额：
$ 38.12万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-10 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9900713
关键词：
Address Adult Anopheles Genus Anopheles gambiae Basic Science Biological Assay Biology Capsid Proteins Cell Line Culicidae Data Densovirus Development Economics Failure Family Female Gene Delivery Gene Expression Genes Genetic Genetic Materials Genome Human Immune Infection Infectious Agent Introns Laboratories Longevity Malaria Male Genital Organs Mediating Methodology MicroRNAs Morbidity - disease rate Mosquito Control Oocysts Parasites Partner in relationship Parvovirus Pathway interactions Pattern Phenotype Plasmids Plasmodium Plasmodium falciparum Population Promoter Regions Publishing Reproductive system Research Salivary Glands Single Stranded DNA Virus Sporozoites Structure System Techniques Technology Tissues Transduction Gene Transfection Transgenes Transgenic Organisms Tropism Vector-transmitted infectious disease Viral Viral Genome Virion Virus base fitness forward genetics in vivo interest knock-down male mortality novel novel strategies offspring overexpression reverse genetics success tool transgene expression transmission process vector vector competence vector mosquito

项目摘要

Project Summary Human malaria, responsible for inordinate mortality, morbidity and economic loss worldwide, is caused by protozoan parasites in the genus Plasmodium that are obligatorily transmitted by Anopheles mosquitoes. Failure of traditional control methodologies has stimulated efforts to develop novel strategies to control the mosquito vectors of malaria, particularly An. gambiae. While transgenic manipulation of Anopheles species has been accomplished, routine manipulation of An. gambiae has proven challenging, and the technology to do so is not broadly available among non-specialized laboratories. The development of novel, easy to use tools for routine forward genetics in An. gambiae is critical for both applied strategies for malaria control and basic research into the genetics and host/parasite interactions of this important mosquito vector species. Densonucleosis viruses, or “densoviruses” (DNVs), are single-stranded DNA viruses in the family Parvoviridae with very small genomes (4-6 kb) that are flanked by terminal hairpin structures at the 5-prime and 3-prime ends. The entire viral genome can be placed into an infectious plasmid from which functional virus will be produced upon transfection into an appropriate cell line. In our laboratory, we have identified only known densovirus (AgDNV) capable of infection and dissemination in Anopheles gambiae. AgDNV replicates preferentially in adult mosquito tissues to very high titer, but is completely non-pathogenic. We have developed and validated novel techniques to use AgDNV to express secreted effectors or microRNAs that can modulate or alter patterns of Anopheles gene expression. Our overall hypothesis is that AgDNV can be used overexpress or knock down expression of specific genes of interest in Anopheles gambiae, leading to phenotypes of basic and applied importance. This overall hypothesis will be addressed in the following specific aims: 1) Develop an AgDNV-based gene transduction system for routine forward genetics in An. gambiae, focusing on modulation of Plasmodium falciparum infection/transmission; 2) Develop an AgDNV-based system for routine reverse genetics in Anopheles gambiae, focusing on modulation of P. falciparum infection/transmission and mosquito fitness; 3) Characterize and quantify AgDNV infection of the male mosquito reproductive system, and determine the potential for using auto-dissemination to introduce AgDNV into mosquito cage populations. This research will result in the development of a novel toolset for addressing basic questions in Anopheles and Plasmodium biology, as well as the development of potential control agents for human malaria.

项目总结