Gene drive-based population suppression in the malaria vector Anopheles stephensi

Xuejiao Xu (), Jingheng Chen, You Wang, Yiran Liu, Yongjie Zhang, Jie Yang, Xiaozhen Yang, Bin Chen, Zhengbo He () and Jackson Champer ()
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Xuejiao Xu: Peking University
Jingheng Chen: Peking University
You Wang: Chongqing Normal University
Yiran Liu: Peking University
Yongjie Zhang: Chongqing Normal University
Jie Yang: Peking University
Xiaozhen Yang: Peking University
Bin Chen: Chongqing Normal University
Zhengbo He: Chongqing Normal University
Jackson Champer: Peking University

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: Abstract Gene drives are alleles that can bias the inheritance of specific traits in target populations for the purpose of modification or suppression. Here, we construct a homing suppression drive in the major urban malaria vector Anopheles stephensi targeting the female-specific exon of doublesex, incorporating two gRNAs and a nanos-Cas9 to reduce functional resistance and improve female heterozygote fitness. Our results show that the drive was recessive sterile in both females and males, with various intersex phenotypes in drive homozygotes. Both male and female drive heterozygotes show only moderate drive conversion, indicating that the nanos promoter has lower activity in A. stephensi than in Anopheles gambiae. By amplicon sequencing, we detect a very low level of resistance allele formation. Combination of the homing suppression drive and a vasa-Cas9 line boosts the drive conversion rate of the homing drive to 100%, suggesting the use of similar systems for population suppression in a continuous release strategy with a lower release rate than SIT or fsRIDL techniques. This study contributes valuable insights to the development of more efficient and environmentally friendly pest control tools aimed at disrupting disease transmission.

Date: 2025
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DOI: 10.1038/s41467-025-56290-2

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