CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus

Harvey-Samuel, Tim; Feng, Xuechun; Okamoto, Emily M.; Purusothaman, Deepak-Kumar; Leftwich, Philip T.; Alphey, Luke; Gantz, Valentino M.

Abstract

Culex mosquitoes pose a significant public health threat as vectors for a variety of diseases including West Nile virus and lymphatic filariasis, and transmit pathogens threatening livestock, companion animals, and endangered birds. Rampant insecticide resistance makes controlling these mosquitoes challenging and necessitates the development of new control strategies. Gene drive technologies have made significant progress in other mosquito species, although similar advances have been lagging in Culex. Here we test a CRISPR-based homing gene drive for Culex quinquefasciatus, and show that the inheritance of two split-gene-drive transgenes, targeting different loci, are biased in the presence of a Cas9-expressing transgene although with modest efficiencies. Our findings extend the list of disease vectors where engineered homing gene drives have been demonstrated to include Culex alongside Anopheles and Aedes, and pave the way for future development of these technologies to control Culex mosquitoes.

Citation

Harvey-Samuel, T., Feng, X., Okamoto, E. M., Purusothaman, D.-K., Leftwich, P. T., Alphey, L., & Gantz, V. M. (in press). CRISPR-based gene drives generate super-Mendelian inheritance in the disease vector Culex quinquefasciatus. Nature communications, 14(1), Article 7561. https://doi.org/10.1038/s41467-023-41834-1

• Journal Article Type: Article
• Acceptance Date: Sep 21, 2023
• Online Publication Date: Nov 20, 2023
• Deposit Date: Feb 24, 2025
• Journal: Nature Communications
• Print ISSN: 2041-1723
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 1
• Article Number: 7561
• DOI: https://doi.org/10.1038/s41467-023-41834-1
• Public URL: https://keele-repository.worktribe.com/output/1078927
• Publisher URL: https://www.nature.com/articles/s41467-023-41834-1
• Additional Information: Received: 12 June 2023; Accepted: 21 September 2023; First Online: 20 November 2023; : V.M.G. is a founder of and has equity interests in Symbol, Inc. and Agragene, Inc., companies that may potentially benefit from the research results described in this manuscript. V.M.G. also serves on both the company’s Scientific Advisory Board and the Board of Directors of Synbal, Inc. 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. L.A. is an advisor to, and has financial or equity interest in, Synvect Inc. and Biocentis Ltd., companies operating in the area of genetic control of pest insects. X.F., T.H.-S., D.-K.P., P.T.L., and E.M.O. declare no competing interests.