Published January 30, 2024 | Version Published
Journal Article Open

Targeting sex determination to suppress mosquito populations

Abstract

Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next-generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Ae. aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to effectively control wild populations of disease vectors.

Copyright and License

© 2023, Li et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Acknowledgement

We thank Judy Ishikawa for helping with mosquito husbandry and Shih-Che Weng for assistance with DNA/RNA extractions. This work was supported in part by funding from NIH (R01AI151004, R01GM132825, RO1AI148300, RO1AI175152, DP2AI152071), EPA STAR award (RD84020401), and an Open Philanthropy award (309937-0001) awarded to OSA; and the U.S. Army Research Office for the Institute for Collaborative Biotechnologies (W911NF-19-2-0026) and NIH (R01-AI165575) awards to CM; and a NIH (1R01AI143698-01A1) award to JMM. The views, opinions, and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the U.S. government.

The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.

Contributions

Ming Li, Conceptualization, Data curation, Formal analysis, Supervision, Validation, Investigation, Methodology, Writing – original draft, Writing – review and editing; Nikolay P Kandul, Data curation, Investigation, Writing – original draft; Ruichen Sun, Formal analysis, Writing – original draft, Writing – review and editing; Ting Yang, Daniel J Brogan, Formal analysis; Elena D Benetta, Igor Antoshechkin, Héctor M Sánchez C, Nicolas A DeBeaubien, YuMin M Loh, Matthew P Su, Data curation, Formal analysis; Yinpeng Zhan, Data curation, Investigation; Craig Montell, Formal analysis, Funding acquisition, Writing – review and editing; John M Marshall, Formal analysis, Funding acquisition; Omar S Akbari, Conceptualization, Supervision, Funding acquisition, Investigation, Writing – original draft, Project administration, Writing – review and editing

Ethics

 All animals were handled in accordance with the Guide for the Care and Use of Laboratory Animals as recommended by the National Institutes of Health and approved by the UCSD Institutional Animal Care and Use Committee (IACUC, Animal Use Protocol #S17187) and UCSD Biological Use Authorization (BUA #R2401).

Conflict of Interest

Ming Li, Nikolay P Kandul: A founder of Synvect with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. Omar S Akbari: A founder of Agragene, Inc with equity interest. A founder of Synvect with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. The other authors declare that no competing interests exist.

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Additional details

Funding

National Institutes of Health
R01AI151004
National Institutes of Health
R01GM132825
National Institutes of Health
RO1AI148300
National Institutes of Health
RO1AI175152
National Institutes of Health
DP2AI152071
Environmental Protection Agency
RD84020401
Open Philanthropy Project
309937-0001
United States Army Research Office
W911NF-19-2-0026
National Institutes of Health
R01-AI165575
National Institutes of Health
1R01AI143698-01A1