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

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,...

Full description

Saved in:
Bibliographic Details
Main Authors: Xuejiao Xu, Jingheng Chen, You Wang, Yiran Liu, Yongjie Zhang, Jie Yang, Xiaozhen Yang, Bin Chen, Zhengbo He, Jackson Champer
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56290-2
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832585555600211968
author Xuejiao Xu
Jingheng Chen
You Wang
Yiran Liu
Yongjie Zhang
Jie Yang
Xiaozhen Yang
Bin Chen
Zhengbo He
Jackson Champer
author_facet Xuejiao Xu
Jingheng Chen
You Wang
Yiran Liu
Yongjie Zhang
Jie Yang
Xiaozhen Yang
Bin Chen
Zhengbo He
Jackson Champer
author_sort Xuejiao Xu
collection DOAJ
description 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.
format Article
id doaj-art-34f3181fb36e410ba991230369d4cabc
institution Kabale University
issn 2041-1723
language English
publishDate 2025-01-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-34f3181fb36e410ba991230369d4cabc2025-01-26T12:42:32ZengNature PortfolioNature Communications2041-17232025-01-0116111010.1038/s41467-025-56290-2Gene drive-based population suppression in the malaria vector Anopheles stephensiXuejiao Xu0Jingheng Chen1You Wang2Yiran Liu3Yongjie Zhang4Jie Yang5Xiaozhen Yang6Bin Chen7Zhengbo He8Jackson Champer9Center for Bioinformatics, Center for Life Sciences, School of Life Sciences, Peking UniversityCenter for Bioinformatics, Center for Life Sciences, School of Life Sciences, Peking UniversityChongqing Key Laboratory of Vector Insects, Institute of Entomology and Molecular Biology, Chongqing Normal UniversityCenter for Bioinformatics, Center for Life Sciences, School of Life Sciences, Peking UniversityChongqing Key Laboratory of Vector Insects, Institute of Entomology and Molecular Biology, Chongqing Normal UniversityCenter for Bioinformatics, Center for Life Sciences, School of Life Sciences, Peking UniversityCenter for Bioinformatics, Center for Life Sciences, School of Life Sciences, Peking UniversityChongqing Key Laboratory of Vector Insects, Institute of Entomology and Molecular Biology, Chongqing Normal UniversityChongqing Key Laboratory of Vector Insects, Institute of Entomology and Molecular Biology, Chongqing Normal UniversityCenter for Bioinformatics, Center for Life Sciences, School of Life Sciences, Peking UniversityAbstract 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.https://doi.org/10.1038/s41467-025-56290-2
spellingShingle Xuejiao Xu
Jingheng Chen
You Wang
Yiran Liu
Yongjie Zhang
Jie Yang
Xiaozhen Yang
Bin Chen
Zhengbo He
Jackson Champer
Gene drive-based population suppression in the malaria vector Anopheles stephensi
Nature Communications
title Gene drive-based population suppression in the malaria vector Anopheles stephensi
title_full Gene drive-based population suppression in the malaria vector Anopheles stephensi
title_fullStr Gene drive-based population suppression in the malaria vector Anopheles stephensi
title_full_unstemmed Gene drive-based population suppression in the malaria vector Anopheles stephensi
title_short Gene drive-based population suppression in the malaria vector Anopheles stephensi
title_sort gene drive based population suppression in the malaria vector anopheles stephensi
url https://doi.org/10.1038/s41467-025-56290-2
work_keys_str_mv AT xuejiaoxu genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi
AT jinghengchen genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi
AT youwang genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi
AT yiranliu genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi
AT yongjiezhang genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi
AT jieyang genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi
AT xiaozhenyang genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi
AT binchen genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi
AT zhengbohe genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi
AT jacksonchamper genedrivebasedpopulationsuppressioninthemalariavectoranophelesstephensi