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A transcomplementing gene drive provides a flexible platform for laboratory investigation and potential field deployment

Author

Listed:
  • Víctor López Del Amo

    (University of California San Diego)

  • Alena L. Bishop

    (University of California San Diego)

  • Héctor M. Sánchez C.

    (University of California)

  • Jared B. Bennett

    (University of California)

  • Xuechun Feng

    (University of California San Diego)

  • John M. Marshall

    (University of California)

  • Ethan Bier

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

  • Valentino M. Gantz

    (University of California San Diego)

Abstract

CRISPR-based gene drives can spread through wild populations by biasing their own transmission above the 50% value predicted by Mendelian inheritance. These technologies offer population-engineering solutions for combating vector-borne diseases, managing crop pests, and supporting ecosystem conservation efforts. Current technologies raise safety concerns for unintended gene propagation. Herein, we address such concerns by splitting the drive components, Cas9 and gRNAs, into separate alleles to form a trans-complementing split–gene-drive (tGD) and demonstrate its ability to promote super-Mendelian inheritance of the separate transgenes. This dual-component configuration allows for combinatorial transgene optimization and increases safety by restricting escape concerns to experimentation windows. We employ the tGD and a small–molecule-controlled version to investigate the biology of component inheritance and resistant allele formation, and to study the effects of maternal inheritance and impaired homology on efficiency. Lastly, mathematical modeling of tGD spread within populations reveals potential advantages for improving current gene-drive technologies for field population modification.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13977-7
    DOI: 10.1038/s41467-019-13977-7
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    Cited by:

    1. Alena L. Bishop & Víctor López Del Amo & Emily M. Okamoto & Zsolt Bodai & Alexis C. Komor & Valentino M. Gantz, 2022. "Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. 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.
    3. Sebald A. N. Verkuijl & Estela Gonzalez & Ming Li & Joshua X. D. Ang & Nikolay P. Kandul & Michelle A. E. Anderson & Omar S. Akbari & Michael B. Bonsall & Luke Alphey, 2022. "A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    4. Michelle A. E. Anderson & Estela Gonzalez & Matthew P. Edgington & Joshua X. D. Ang & Deepak-Kumar Purusothaman & Lewis Shackleford & Katherine Nevard & Sebald A. N. Verkuijl & Timothy Harvey-Samuel &, 2024. "A multiplexed, confinable CRISPR/Cas9 gene drive can propagate in caged Aedes aegypti populations," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Frieß, Johannes L. & Lalyer, Carina R. & Giese, Bernd & Simon, Samson & Otto, Mathias, 2023. "Review of gene drive modelling and implications for risk assessment of gene drive organisms," Ecological Modelling, Elsevier, vol. 478(C).

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