G protein-coupled receptors (GPCRs), key regulators of a variety of critical biological processes, are attractive targets for insecticide development. Given the importance of these receptors in many organisms, including humans, it is critical that novel pesticides directed against GPCRs are designed to be species-specific. Here, we present characterization of an interfering RNA pesticide (IRP) targeting the mosquito GPCR-encoding dopamine 1 receptor (dop1) genes. A small interfering RNA corresponding to dop1 was identified in a screen for IRPs that kill Aedes aegypti during both the adult and larval stages. The 25 bp sequence targeted by this IRP is conserved in the dop1 genes of multiple mosquito species, but not in non-target organisms, indicating that it could function as a biorational mosquito insecticide. Aedes aegypti adults treated through microinjection or attractive toxic sugar bait delivery of small interfering RNA corresponding to the target site exhibited severe neural and behavioral defects and high levels of adult mortality. Likewise, A. aegypti larval consumption of dried inactivated yeast tablets prepared from a Saccharomyces cerevisiae strain engineered to express short hairpin RNA corresponding to the dop1 target site resulted in severe neural defects and larval mortality. Aedes albopictus and Anopheles gambiae adult and larval mortality was also observed following treatment with dop1 IRPs, which were not toxic to non-target arthropods. The results of this investigation indicate that dop1 IRPs can be used for species-specific targeting of dop1 GPCRs and may represent a new biorational strategy for control of both adult and larval mosquitoes.

G 蛋白偶联受体 (GPCR) 是各种关键生物过程的关键调节剂，是杀虫剂开发的有吸引力的目标。鉴于这些受体在包括人类在内的许多生物体中的重要性，针对 GPCR 的新型杀虫剂必须设计为具有物种特异性。在这里，我们提出了针对蚊子 GPCR 编码多巴胺 1 受体 (dop1)基因的干扰 RNA 农药 (IRP) 的表征。在筛选 IRPs 时发现了一个与dop1相对应的小干扰 RNA ，该 IRPs在成虫和幼虫阶段都杀死了埃及伊蚊。此 IRP 所针对的 25 bp 序列在dop1 中保存多种蚊子的基因，但在非目标生物中没有，表明它可以作为一种生物合理的蚊虫杀虫剂。通过显微注射或有吸引力的有毒糖诱饵递送与目标部位相对应的小干扰 RNA 治疗的埃及伊蚊成人表现出严重的神经和行为缺陷以及高水平的成人死亡率。同样，A. aegypti幼虫消耗由酿酒酵母菌株制备的干燥灭活酵母片，该菌株经工程改造以表达对应于dop1靶位点的短发夹 RNA，导致严重的神经缺陷和幼虫死亡。白纹伊蚊和冈比亚按蚊在使用对非靶标节肢动物无毒的dop1 IRP治疗后也观察到成虫和幼虫死亡率。这项调查的结果表明，dop1 IRP 可用于针对特定物种的dop1 GPCR，并可能代表一种新的控制成蚊和幼蚊的生物合理策略。