Closing the gap to effective gene drive in Aedes aegypti by exploiting germline regulatory elements

Anderson, Michelle A. E.; Gonzalez, Estela; Ang, Joshua X. D.; Shackleford, Lewis; Nevard, Katherine; Verkuijl, Sebald A. N.; Edgington, Matthew P.; Harvey-Samuel, Tim; Alphey, Luke

Abstract

CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. While attempts have been made to develop such systems in Aedes aegypti, none have been able to match the high drive efficiency observed in Anopheles species. Here we generate Ae. aegypti transgenic lines expressing Cas9 using germline-specific regulatory elements and assess their ability to bias inheritance of an sgRNA-expressing element (kmosgRNAs). Four shu-Cas9 and one sds3-Cas9 isolines can significantly bias the inheritance of kmosgRNAs, with sds3G1-Cas9 causing the highest average inheritance of ~86% and ~94% from males and females carrying both elements outcrossed to wild-type, respectively. Our mathematical model demonstrates that sds3G1-Cas9 could enable the spread of the kmosgRNAs element to either reach a higher (by ~15 percentage point) maximum carrier frequency or to achieve similar maximum carrier frequency faster (by 12 generations) when compared to two other established split drive systems.

Citation

Anderson, M. A. E., Gonzalez, E., Ang, J. X. D., Shackleford, L., Nevard, K., Verkuijl, S. A. N., Edgington, M. P., Harvey-Samuel, T., & Alphey, L. (in press). Closing the gap to effective gene drive in Aedes aegypti by exploiting germline regulatory elements. Nature communications, 14(1), Article 338. https://doi.org/10.1038/s41467-023-36029-7

• Journal Article Type: Article
• Acceptance Date: Jan 13, 2023
• Online Publication Date: Jan 20, 2023
• Deposit Date: Feb 24, 2025
• Journal: Nature Communications
• Print ISSN: 2041-1723
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 1
• Article Number: 338
• DOI: https://doi.org/10.1038/s41467-023-36029-7
• Public URL: https://keele-repository.worktribe.com/output/1078906
• Publisher URL: https://www.nature.com/articles/s41467-023-36029-7
• Additional Information: Received: 31 August 2022; Accepted: 13 January 2023; First Online: 20 January 2023; : The authors declare no competing interests.