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

Michelle A. E. Anderson, Estela Gonzalez, Joshua X. D. Ang, Lewis Shackleford, Katherine Nevard, Sebald A. N. Verkuijl, Matthew P. Edgington, Tim Harvey-Samuel and Luke Alphey ()
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Michelle A. E. Anderson: The Pirbright Institute
Estela Gonzalez: The Pirbright Institute
Joshua X. D. Ang: The Pirbright Institute
Lewis Shackleford: The Pirbright Institute
Katherine Nevard: The Pirbright Institute
Sebald A. N. Verkuijl: The Pirbright Institute
Matthew P. Edgington: The Pirbright Institute
Tim Harvey-Samuel: The Pirbright Institute
Luke Alphey: The Pirbright Institute

Nature Communications, 2023, vol. 14, issue 1, 1-9

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36029-7

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