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A genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression

Author

Listed:
  • Chrysanthi Taxiarchi

    (Imperial College London)

  • Andrea Beaghton

    (Imperial College London)

  • Nayomi Illansinhage Don

    (Imperial College London)

  • Kyros Kyrou

    (Imperial College London)

  • Matthew Gribble

    (Imperial College London)

  • Dammy Shittu

    (Imperial College London)

  • Scott P. Collins

    (North Carolina State University)

  • Chase L. Beisel

    (North Carolina State University
    Helmholtz-Centre for Infection Research (HZI)
    University of Würzburg)

  • Roberto Galizi

    (Keele University)

  • Andrea Crisanti

    (Imperial College London
    University of Padova)

Abstract

CRISPR-based gene drives offer promising means to reduce the burden of pests and vector-borne diseases. These techniques consist of releasing genetically modified organisms carrying CRISPR-Cas nucleases designed to bias their inheritance and rapidly propagate desired modifications. Gene drives can be intended to reduce reproductive capacity of harmful insects or spread anti-pathogen effectors through wild populations, even when these confer fitness disadvantages. Technologies capable of halting the spread of gene drives may prove highly valuable in controlling, counteracting, and even reverting their effect on individual organisms as well as entire populations. Here we show engineering and testing of a genetic approach, based on the germline expression of a phage-derived anti-CRISPR protein (AcrIIA4), able to inactivate CRISPR-based gene drives and restore their inheritance to Mendelian rates in the malaria vector Anopheles gambiae. Modeling predictions and cage testing show that a single release of male mosquitoes carrying the AcrIIA4 protein can block the spread of a highly effective suppressive gene drive preventing population collapse of caged malaria mosquitoes.

Suggested Citation

  • Chrysanthi Taxiarchi & Andrea Beaghton & Nayomi Illansinhage Don & Kyros Kyrou & Matthew Gribble & Dammy Shittu & Scott P. Collins & Chase L. Beisel & Roberto Galizi & Andrea Crisanti, 2021. "A genetically encoded anti-CRISPR protein constrains gene drive spread and prevents population suppression," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24214-5
    DOI: 10.1038/s41467-021-24214-5
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    Cited by:

    1. Sara Sanz Juste & Emily M. Okamoto & Christina Nguyen & Xuechun Feng & Víctor López Del Amo, 2023. "Next-generation CRISPR gene-drive systems using Cas12a nuclease," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    2. Shicong Du & Xinzhao Tong & Alvin C. K. Lai & Chak K. Chan & Christopher E. Mason & Patrick K. H. Lee, 2023. "Highly host-linked viromes in the built environment possess habitat-dependent diversity and functions for potential virus-host coevolution," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Rocco D’Amato & Chrysanthi Taxiarchi & Marco Galardini & Alessandro Trusso & Roxana L. Minuz & Silvia Grilli & Alastair G. T. Somerville & Dammy Shittu & Ahmad S. Khalil & Roberto Galizi & Andrea Cris, 2024. "Anti-CRISPR Anopheles mosquitoes inhibit gene drive spread under challenging behavioural conditions in large cages," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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