Plasmodium relies on numerous agonists during its journey through the mosquito vector, and these agonists represent potent targets for transmission-blocking by either inhibiting or interfering with them pre- or post-transcriptionally. The recently developed CRISPR/Cas9-based genome editing tools for Anopheles mosquitoes provide new and promising opportunities for the study of agonist function and for developing malaria control strategies through gene deletion to achieve complete agonist inactivation. Here we have established a modified CRISPR/Cas9 gene editing procedure for the malaria vector Anopheles gambiae, and studied the effect of inactivating the fibrinogen-related protein 1 (FREP1) gene on the mosquito’s susceptibility to Plasmodium and on mosquito fitness. FREP1 knockout mutants developed into adult mosquitoes that showed profound suppression of infection with both human and rodent malaria parasites at the oocyst and sporozoite stages. FREP1 inactivation, however, resulted in fitness costs including a significantly lower blood-feeding propensity, fecundity and egg hatching rate, a retarded pupation time, and reduced longevity after a blood meal.

疟原虫在通过蚊媒的过程中依赖多种激动剂，这些激动剂通过在转录前或转录后抑制或干扰它们，代表了有效的传递阻断靶标。最近为蚊子按蚊开发的基于CRISPR / Cas9的基因组编辑工具为激动剂功能的研究以及通过基因缺失实现完全激动剂失活发展疟疾控制策略提供了新的和有希望的机会。在这里，我们为疟疾媒介冈比亚按蚊建立了修改后的CRISPR / Cas9基因编辑程序，并研究了灭活纤维蛋白原相关蛋白1（FREP1）基因对蚊子易感性的影响。疟原虫和对蚊子的健身。FREP 1基因敲除突变体发展成成年蚊子，在卵囊和子孢子阶段对人和啮齿类疟疾寄生虫的感染均表现出了显着的抑制作用。但是，FREP1的失活导致健身成本降低，包括显着降低采血倾向，繁殖力和卵孵化率，化脓时间延迟以及血餐后寿命降低。