Published April 20, 2023 | Version Submitted + Supplemental Material
Discussion Paper Open

Targeting Sex Determination to Suppress Mosquito Populations

  • 1. ROR icon University of California, San Diego
  • 2. ROR icon California Institute of Technology
  • 3. ROR icon University of California, Berkeley
  • 4. ROR icon University of California, Santa Barbara
  • 5. ROR icon Nagoya University
  • 6. ROR icon Innovative Genomics Institute

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 Aedes 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 control wild populations, safely curtailing disease transmission.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. We thank Judy Ishikawa for helping with mosquito husbandry and Shi-Che Weng for assistance with DNA/RNA extractions. This work was supported in part by funding from NIH (R01AI151004, DP2AI152071, R01GM132825), EPA (Award #RD84020401), and Open Philanthropy (309937-0001) awards 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. Data availability. Complete sequence maps assembled in the study are deposited at 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 the Supplementary Materials/Source Data files (Supplementary Tables 1–11). Aedes transgenic lines are available upon request. Source data is provided with this paper. Competing Interest Statement. O.S.A. is a founder of Agragene, Inc. with equity interest. O.S.A., M.L., and N.P.K are founders 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. All remaining authors declare no competing interests.

Attached Files

Submitted - nihpp-2023.04.18.537404v1.pdf

Supplemental Material - media-1.xlsx

Supplemental Material - media-2.docx

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Additional details

Identifiers

PMCID
PMC10153225
Eprint ID
122028
Resolver ID
CaltechAUTHORS:20230628-257149000.30

Funding

NIH
R01AI151004
NIH
DP2AI152071
NIH
R01GM132825
Environmental Protection Agency (EPA)
RD84020401
Open Philanthropy
309937-0001
Army Research Office (ARO)
W911NF-19-2-0026
NIH
R01-AI165575
NIH
1R01AI143698-01A1

Dates

Created
2023-06-29
Created from EPrint's datestamp field
Updated
2023-06-29
Created from EPrint's last_modified field