IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29868-3.html
   My bibliography  Save this article

Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles

Author

Listed:
  • Alena L. Bishop

    (University of California San Diego)

  • Víctor López Del Amo

    (University of California San Diego)

  • Emily M. Okamoto

    (University of California San Diego)

  • Zsolt Bodai

    (University of California San Diego)

  • Alexis C. Komor

    (University of California San Diego)

  • Valentino M. Gantz

    (University of California San Diego)

Abstract

Homing CRISPR gene drives could aid in curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations due to an inheritance rate that surpasses Mendelian laws. However, this technology suffers from resistance alleles formed when the drive-induced DNA break is repaired by error-prone pathways, which creates mutations that disrupt the gRNA recognition sequence and prevent further gene-drive propagation. Here, we attempt to counteract this by encoding additional gRNAs that target the most commonly generated resistance alleles into the gene drive, allowing a second opportunity at gene-drive conversion. Our presented “double-tap” strategy improved drive efficiency by recycling resistance alleles. The double-tap drive also efficiently spreads in caged populations, outperforming the control drive. Overall, this double-tap strategy can be readily implemented in any CRISPR-based gene drive to improve performance, and similar approaches could benefit other systems suffering from low HDR frequencies, such as mammalian cells or mouse germline transformations.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29868-3
    DOI: 10.1038/s41467-022-29868-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29868-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29868-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Andrew Hammond & Paola Pollegioni & Tania Persampieri & Ace North & Roxana Minuz & Alessandro Trusso & Alessandro Bucci & Kyros Kyrou & Ioanna Morianou & Alekos Simoni & Tony Nolan & Ruth Müller & And, 2021. "Gene-drive suppression of mosquito populations in large cages as a bridge between lab and field," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    2. 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.
    3. 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.
    4. Megan Scudellari, 2019. "Self-destructing mosquitoes and sterilized rodents: the promise of gene drives," Nature, Nature, vol. 571(7764), pages 160-162, July.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Lukas Möller & Eric J. Aird & Markus S. Schröder & Lena Kobel & Lucas Kissling & Lilly van de Venn & Jacob E. Corn, 2022. "Recursive Editing improves homology-directed repair through retargeting of undesired outcomes," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. 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.
    3. 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.
    4. Alejo Menchaca, 2021. "Sustainable Food Production: The Contribution of Genome Editing in Livestock," Sustainability, MDPI, vol. 13(12), pages 1-16, June.
    5. Angela Meccariello & Shibo Hou & Serafima Davydova & James Daniel Fawcett & Alexandra Siddall & Philip T. Leftwich & Flavia Krsticevic & Philippos Aris Papathanos & Nikolai Windbichler, 2024. "Gene drive and genetic sex conversion in the global agricultural pest Ceratitis capitata," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    6. 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).
    7. Penelope A. Hancock & Ace North & Adrian W. Leach & Peter Winskill & Azra C. Ghani & H. Charles J. Godfray & Austin Burt & John D. Mumford, 2024. "The potential of gene drives in malaria vector species to control malaria in African environments," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    8. Jones, Michael S. & Brown, Zachary S., 2023. "Food for thought: Assessing the consumer welfare impacts of deploying irreversible, landscape-scale biotechnologies," Food Policy, Elsevier, vol. 121(C).
    9. Sarah Hartley & Adam Kokotovich & Caroline McCalman, 2023. "Prescribing engagement in environmental risk assessment for gene drive technology," Regulation & Governance, John Wiley & Sons, vol. 17(2), pages 411-424, April.
    10. Charlotte Douglas & Valdone Maciulyte & Jasmin Zohren & Daniel M. Snell & Shantha K. Mahadevaiah & Obah A. Ojarikre & Peter J. I. Ellis & James M. A. Turner, 2021. "CRISPR-Cas9 effectors facilitate generation of single-sex litters and sex-specific phenotypes," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    11. Hartley, Sarah & Ledingham, Katie & Owen, Richard & Leonelli, Sabina & Diarra, Samba & Diop, Samba, 2021. "Experimenting with co-development: A qualitative study of gene drive research for malaria control in Mali," Social Science & Medicine, Elsevier, vol. 276(C).
    12. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29868-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.