蚊媒病一直是危害人类健康的重要公共卫生问题。近年来，全球不断有新的蚊媒病爆发（如寨卡病毒），蚊媒病的有效防控迫在眉睫。化学防制一直是媒介防制规划中的主要方法，然而蚊媒已对多种化学和生物杀虫剂产生抗性。因此研发可替代的新型杀虫剂, 尤其是寻找疾病传播媒介雌蚊繁殖势能调控的新方法，已成为目前媒介防制所面临的一大难题。申请人在上一个国家自然科学基金资助下，发现蛋白酶体催化亚单位（PSMB）在蚊特定阶段和部位表达，抑制蛋白酶体催化亚单位6表达能明显降低雌蚊的生殖力。本项目拟进一步研究PSMB在蚊生殖功能中的作用，采用CRISPR-Cas9系统构建PSMB敲除的转基因蚊，验证PSMB对蚊生殖功能的影响；并在半现场条件下观察PSMB抑制对靶标蚊的种群抑制效果。本研究的预期结果可望为研发基于直接控制雌蚊繁殖势能的新型无污染生物杀虫剂奠定基础，为蚊媒综合防制提供一种全新方法。

Mosquito-borne diseases cause serious mortality and morbidity in humans, and pose significant threats to public health. Recent years, there has been new outbreaks of mosquito-borne diseases (such as zika virus) around the world. Vector control is the primary method for controlling and preventing mosquito-borne diseases. The widely use of pesticide had resulted in the emergence and spread of resistance in mosquito populations. There is urgent needs for effective prevention and vector control strategies and tools. Only female mosquitoes are responsible for blood sucking and disease transmission. Research and develop new pesticide targeting female reproductive potential could be an efficient way for mosquito population suppression and mosquito-borne disease prevention.Our previous researches pointed out that proteasome subunit was only expressed at female abdomen and dsRNA based RNA interference targeting proteasome subunit resulted in reduced fertility in mosquitoes,suggesting that proteasome subunit play important roles in female reproduction. The central objectives of this new application are to examine the role of proteasome subunit in female mosquito reproduction and to evaluate the possibility of reaching population suppression by decreasing female fertility. The specific aims are: 1) to exam the function of proteasome subunitm in female reproduction using CRISPR-Cas9-mediated gene drive system, dsRNA interference system and pharmceutical inhibitors; and 2) to evaluated the efficacy of inhibiting female fertility on population suppression using semi-field experiment. We anticipated that the knowledge from this application will greatly facilitate the development of innovative strategies and tools for vector controlling management and help with vector-borne disease elimination.