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Improving the suppressive power of homing gene drive by co-targeting a distant-site female fertility gene

Author

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  • Nicky R. Faber

    (Wageningen University & Research)

  • Xuejiao Xu

    (Center for Life Sciences, Peking University)

  • Jingheng Chen

    (Center for Life Sciences, Peking University)

  • Shibo Hou

    (Center for Life Sciences, Peking University)

  • Jie Du

    (Center for Life Sciences, Peking University)

  • Bart A. Pannebakker

    (Wageningen University & Research)

  • Bas J. Zwaan

    (Wageningen University & Research)

  • Joost Heuvel

    (Wageningen University & Research)

  • Jackson Champer

    (Center for Life Sciences, Peking University)

Abstract

Gene drive technology has the potential to address major biological challenges. Well-studied homing suppression drives have been shown to be highly efficient in Anopheles mosquitoes, but for other organisms, lower rates of drive conversion prevent elimination of the target population. To tackle this issue, we propose a gene drive design that has two targets: a drive homing site where drive conversion takes place, and a distant site where cleavage induces population suppression. We model this design and find that the two-target system allows suppression to occur over a much wider range of drive conversion efficiency. Specifically, the cutting efficiency now determines the suppressive power of the drive, rather than the conversion efficiency as in standard suppression drives. We construct a two-target drive in Drosophila melanogaster and show that both components of the gene drive function successfully. However, cleavage in the embryo from maternal deposition as well as fitness costs in female drive heterozygotes both remain significant challenges for both two-target and standard suppression drives. Overall, our improved gene drive design has the potential to ease problems associated with homing suppression gene drives for many species where drive conversion is less efficient.

Suggested Citation

  • Nicky R. Faber & Xuejiao Xu & Jingheng Chen & Shibo Hou & Jie Du & Bart A. Pannebakker & Bas J. Zwaan & Joost Heuvel & Jackson Champer, 2024. "Improving the suppressive power of homing gene drive by co-targeting a distant-site female fertility gene," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53631-5
    DOI: 10.1038/s41467-024-53631-5
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    References listed on IDEAS

    as
    1. Hannah A. Grunwald & Valentino M. Gantz & Gunnar Poplawski & Xiang-Ru S. Xu & Ethan Bier & Kimberly L. Cooper, 2019. "Super-Mendelian inheritance mediated by CRISPR–Cas9 in the female mouse germline," Nature, Nature, vol. 566(7742), pages 105-109, February.
    2. Kevin M Esvelt & Neil J Gemmell, 2017. "Conservation demands safe gene drive," PLOS Biology, Public Library of Science, vol. 15(11), pages 1-8, November.
    3. Jie Du & Weizhe Chen & Xihua Jia & Xuejiao Xu & Emily Yang & Ruizhi Zhou & Yuqi Zhang & Matt Metzloff & Philipp W. Messer & Jackson Champer, 2024. "Germline Cas9 promoters with improved performance for homing gene drive," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
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