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Homing gene drives can transfer rapidly between Anopheles gambiae strains with minimal carryover of flanking sequences

Author

Listed:
  • Poppy Pescod

    (Liverpool School of Tropical Medicine)

  • Giulia Bevivino

    (University of Rome “la Sapienza”)

  • Amalia Anthousi

    (Liverpool School of Tropical Medicine
    University of Crete, Vassilika Vouton
    Foundation for Research and Technology-Hellas)

  • Josephine Shepherd

    (Liverpool School of Tropical Medicine)

  • Ruth Shelton

    (Liverpool School of Tropical Medicine)

  • Fabrizio Lombardo

    (University of Rome “la Sapienza”)

  • Tony Nolan

    (Liverpool School of Tropical Medicine)

Abstract

CRISPR-Cas9 homing gene drives are designed to induce a targeted double-stranded DNA break at a wild type allele (‘recipient’), which, when repaired by the host cell, is converted to the drive allele from the homologous (‘donor’) chromosome. Germline localisation of this process leads to super-Mendelian inheritance of the drive and the rapid spread of linked traits, offering a novel strategy for population control through the deliberate release of drive individuals. During the homology-based DNA repair, additional segments of the recipient chromosome may convert to match the donor, potentially impacting carrier fitness and strategy success. Using Anopheles gambiae strains with variations around the drive target site, here we assess the extent and nature of chromosomal conversion. We show both homing and meiotic drive contribute as mechanisms of inheritance bias. Additionally, over 80% of homing events resolve within 50 bp of the chromosomal break, enabling rapid gene drive transfer into locally-adapted genetic backgrounds.

Suggested Citation

  • Poppy Pescod & Giulia Bevivino & Amalia Anthousi & Josephine Shepherd & Ruth Shelton & Fabrizio Lombardo & Tony Nolan, 2024. "Homing gene drives can transfer rapidly between Anopheles gambiae strains with minimal carryover of flanking sequences," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51225-9
    DOI: 10.1038/s41467-024-51225-9
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    References listed on IDEAS

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    1. Stephanie L. James & David A. O’Brochta & Filippo Randazzo & Omar S. Akbari, 2023. "A gene drive is a gene drive: the debate over lumping or splitting definitions," Nature Communications, Nature, vol. 14(1), pages 1-3, December.
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    1. Raul F. Medina & Jennifer Kuzma, 2023. "Engineered and natural gene drives: mechanistically the same, yet not same in kind," Nature Communications, Nature, vol. 14(1), pages 1-2, December.

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