Targeting sex determination to suppress mosquito populations
Creators
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1.
California Institute of Technology
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.
Funding
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.
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: Formal analysis
Elena D Benetta: Data curation, Formal analysis
Daniel J Brogan: Formal analysis
Igor Antoshechkin: Data curation, Formal analysis
Héctor M Sánchez C: Data curation, Formal analysis
Yinpeng Zhan: Data curation, Investigation
Nicolas A DeBeaubien: Data curation, Formal analysis
YuMin M Loh: Data curation, Formal analysis
Matthew P Su: Data curation, Formal analysis
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
Data Availability
Complete sequence maps assembled in the study are deposited at https://www.addgene.org/ under ID# 200252 (gRNAdsx, 1067B), 200251 (gRNAix, 1055J), and 200253 (gRNAdsx,ix,βTub, 1067L). Illumina and Nanopore sequencing data have been deposited to the NCBI-SRA under BioProject ID PRJNA942966, SAMN33705824–SAMN33705835; PRJNA942966, SAMN33705934. Data used to generate figures are provided in Supplementary file 1a–k. Aedes transgenic lines are available upon request.
The following dataset was generated:
Li M, Kandul NP, Sun R, Yang T, Benetta ED, Brogan DJ, Antoshechkin I, Sánchez HM, Zhan Y, DeBeaubien NA, Loh YM, Su MP, Montell C, Marshall JM, Akbari OS. 2023. Targeting sex determination to suppress mosquito populations. NCBI BioProject. PRJNA942966
Conflict of Interest
Ming Li: 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
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
Ruichen Sun: No competing interests declared
Ting Yang: No competing interests declared
Elena D Benetta: No competing interests declared
Daniel J Brogan: No competing interests declared
Igor Antoshechkin: No competing interests declared
Héctor M Sánchez C: No competing interests declared
Yinpeng Zhan: No competing interests declared
Nicolas A DeBeaubien: No competing interests declared
YuMin M Loh: No competing interests declared
Matthew P Su: No competing interests declared
Craig Montell: No competing interests declared
John M Marshall: No competing interests declared
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
Files
elife-90199-v1.pdf
Additional details
Identifiers
- PMCID
- PMC10945564
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
- United States Army Research Office
- W911NF-19-2-0026
- National Institutes of Health
- R01-AI165575
- National Institutes of Health
- 1R01AI143698-01A1