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A multiplexed, confinable CRISPR/Cas9 gene drive can propagate in caged Aedes aegypti populations

Author

Listed:
  • Michelle A. E. Anderson

    (Arthropod Genetics, The Pirbright Institute
    University of York, Wentworth Way)

  • Estela Gonzalez

    (Arthropod Genetics, The Pirbright Institute
    Animal and Plant Health Agency, Woodham Lane, Addlestone)

  • Matthew P. Edgington

    (Arthropod Genetics, The Pirbright Institute
    University of York, Wentworth Way)

  • Joshua X. D. Ang

    (Arthropod Genetics, The Pirbright Institute
    University of York, Wentworth Way)

  • Deepak-Kumar Purusothaman

    (Arthropod Genetics, The Pirbright Institute
    MRC-University of Glasgow Centre for Virus Research)

  • Lewis Shackleford

    (Arthropod Genetics, The Pirbright Institute
    University of York, Wentworth Way)

  • Katherine Nevard

    (Arthropod Genetics, The Pirbright Institute)

  • Sebald A. N. Verkuijl

    (Arthropod Genetics, The Pirbright Institute
    University of Oxford)

  • Timothy Harvey-Samuel

    (Arthropod Genetics, The Pirbright Institute)

  • Philip T. Leftwich

    (Arthropod Genetics, The Pirbright Institute
    University of East Anglia, Norwich Research Park, Norwich)

  • Kevin Esvelt

    (Massachusetts Institute of Technology)

  • Luke Alphey

    (Arthropod Genetics, The Pirbright Institute
    University of York, Wentworth Way)

Abstract

Aedes aegypti is the main vector of several major pathogens including dengue, Zika and chikungunya viruses. Classical mosquito control strategies utilizing insecticides are threatened by rising resistance. This has stimulated interest in new genetic systems such as gene drivesHere, we test the regulatory sequences from the Ae. aegypti benign gonial cell neoplasm (bgcn) homolog to express Cas9 and a separate multiplexing sgRNA-expressing cassette inserted into the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene. When combined, these two elements provide highly effective germline cutting at the kmo locus and act as a gene drive. Our target genetic element drives through a cage trial population such that carrier frequency of the element increases from 50% to up to 89% of the population despite significant fitness costs to kmo insertions. Deep sequencing suggests that the multiplexing design could mitigate resistance allele formation in our gene drive system.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44956-2
    DOI: 10.1038/s41467-024-44956-2
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    References listed on IDEAS

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