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Genetic conversion of a split-drive into a full-drive element

Author

Listed:
  • Gerard Terradas

    (University of California, San Diego
    University of California, San Diego
    The Pennsylvania State University)

  • Jared B. Bennett

    (University of California)

  • Zhiqian Li

    (University of California, San Diego
    University of California, San Diego)

  • John M. Marshall

    (University of California
    Innovative Genomics Institute)

  • Ethan Bier

    (University of California, San Diego
    University of California, San Diego)

Abstract

The core components of CRISPR-based gene drives, Cas9 and guide RNA (gRNA), either can be linked within a self-contained single cassette (full gene-drive, fGD) or be provided in two separate elements (split gene-drive, sGD), the latter offering greater control options. We previously engineered split systems that could be converted genetically into autonomous full drives. Here, we examine such dual systems inserted at the spo11 locus that are recoded to restore gene function and thus organismic fertility. Despite minimal differences in transmission efficiency of the sGD or fGD drive elements in single generation crosses, the reconstituted spo11 fGD cassette surprisingly exhibits slower initial drive kinetics than the unlinked sGD element in multigenerational cage studies, but then eventually catches up to achieve a similar level of final introduction. These unexpected kinetic behaviors most likely reflect differing transient fitness costs associated with individuals co-inheriting Cas9 and gRNA transgenes during the drive process.

Suggested Citation

  • Gerard Terradas & Jared B. Bennett & Zhiqian Li & John M. Marshall & Ethan Bier, 2023. "Genetic conversion of a split-drive into a full-drive element," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35044-4
    DOI: 10.1038/s41467-022-35044-4
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    References listed on IDEAS

    as
    1. Víctor López Del Amo & Alena L. Bishop & Héctor M. Sánchez C. & Jared B. Bennett & Xuechun Feng & John M. Marshall & Ethan Bier & Valentino M. Gantz, 2020. "A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    2. Annabel Guichard & Tisha Haque & Marketta Bobik & Xiang-Ru S. Xu & Carissa Klanseck & Raja Babu Singh Kushwah & Mateus Berni & Bhagyashree Kaduskar & Valentino M. Gantz & Ethan Bier, 2019. "Efficient allelic-drive in Drosophila," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    3. Zhiqian Li & Nimi Marcel & Sushil Devkota & Ankush Auradkar & Stephen M. Hedrick & Valentino M. Gantz & Ethan Bier, 2021. "CopyCatchers are versatile active genetic elements that detect and quantify inter-homolog somatic gene conversion," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

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