近日，美国加州大学教授Ethan Bier及其小组的最新研究揭示了驱动蚊子FREP1基因的保护性等位基因来对抗疟疾。相关论文于2025年7月23日发表在《自然》杂志上。

在这里，该研究团队产生了同源的斯氏按蚊菌株，编辑后携带易受寄生虫感染的FREP1L224或推定难耐的FREP1Q224等位基因。FREP1Q224等位基因赋予小鼠抵抗人类和啮齿动物疟疾寄生虫感染的能力，而适应性成本可以忽略不计。保护性的FREP1Q224等位基因可以有效地驱动到FREP1L224蚊子种群中，这是一个新的连锁等位基因驱动系统，该系统选择性地用寄生虫抗性的Q224等位基因取代L224密码子，从而使种群对寄生虫感染具有抗性。这种抗疟疾驱动系统为帮助消除疟疾提供了一种新的遗传方法。

据介绍，疟疾仍然是一个重大的全球健康挑战，每年造成大约50万人死亡。疟原虫感染中肠上皮需要蚊子纤维蛋白原相关蛋白1 （FREP1）。据报道，天然存在的FREP1Q等位基因可以预防寄生虫感染，同时支持蚊子的基本生理功能。

附：英文原文

Title: Driving a protective allele of the mosquito FREP1 gene to combat malaria

Author: Li, Zhiqian, Dong, Yuemei, You, Lang, Corder, Rodrigo M., Arzobal, Jemariz, Yeun, Audrey, Yang, Lei, Marshall, John M., Dimopoulos, George, Bier, Ethan

Issue&Volume: 2025-07-23

Abstract: Malaria remains a substantial global health challenge, causing approximately half a million deaths each year1. The mosquito fibrinogen-related protein 1 (FREP1) is required for malaria parasites to infect the midgut epithelium2. The naturally occurring FREP1Q allele has been reported to prevent parasite infection, while supporting essential physiological functions in the mosquito3. Here we generate congenic strains of Anopheles stephensi, edited to carry either the parasite-susceptible FREP1L224 or the putative-refractory FREP1Q224 alleles. The FREP1Q224 allele confers robust resistance to infection by both human and rodent malaria parasites, with negligible fitness costs. The protective FREP1Q224 allele can be efficiently driven into FREP1L224 mosquito populations using a novel linked allelic-drive system that selectively replaces the L224 codon with the parasite-refractory Q224 allele, thereby rendering populations refractory to parasite infection. This antimalaria drive system provides a novel genetic approach to aid in malaria elimination efforts.

DOI: 10.1038/s41586-025-09283-6

Source: https://www.nature.com/articles/s41586-025-09283-6