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

• 成果类型: Article
• 署名作者: Li, Zhiqian; Dong, Yuemei; You, Lang; Corder, Rodrigo M.; Arzobal, Jemariz; Yeun, Audrey; Yang, Lei; Marshall, John M.; Dimopoulos, George; Bier, Ethan
• 署名单位: University of California System; University of California San Diego; University of California System; University of California San Diego; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; Universidade de Sao Paulo; Institute Biomed Science, University Sao Paulo; University of California System; University of California Berkeley
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2423
• DOI: 10.1038/s41586-025-09283-6
• 发表日期: 2025-09-18
• 关键词: population modification; vector mosquito; end resection; transgenesis; transmission; expression; mechanism; protein

摘要

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.