A population modification gene drive targeting both Saglin and Lipophorin impairs Plasmodium transmission in Anopheles mosquitoes
- Inserm, CNRS, University of Strasbourg, France
Abstract
Lipophorin is an essential, highly expressed lipid transport protein that is secreted and circulates in insect hemolymph. We hijacked the Anopheles coluzzii Lipophorin gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites of the malaria parasite Plasmodium falciparum. The resulting transgenic mosquitoes show a markedly decreased ability to transmit Plasmodium berghei expressing the P. falciparum circumsporozoite protein to mice. To force the spread of this anti-malarial transgene in a mosquito population, we designed and tested several CRISPR/Cas9-based gene drives. One of these is installed in, and disrupts, the pro-parasitic gene Saglin and also cleaves wild-type Lipophorin, causing the anti-malarial modified Lipophorin version to replace the wild type and hitch-hike together with the Saglin drive. Although generating drive-resistant alleles and showing instability in its gRNA-encoding multiplex array, the Saglin-based gene drive reached high levels in caged mosquito populations and efficiently promoted the simultaneous spread of the antimalarial Lipophorin::Sc2A10 allele. This combination is expected to decrease parasite transmission via two different mechanisms. This work contributes to the design of novel strategies to spread antimalarial transgenes in mosquitoes, and illustrates some expected and unexpected outcomes encountered when establishing a population modification gene drive.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file.
Article and author information
Author details
Roenick Proveti Olmo
Funding
ANR (ANR-19-CE35-0007-01)
- Eric Marois
ANR (ANR-11-LABX-0024)
- Stéphanie Blandin
ANR (#ANR-11-EQPX-0022)
- Eric Marois
DFG (#KL 3251/1-1)
- Dennis Klug
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Work on mice was evaluated by the CREMEAS Ethics committee and authorized by Ministère de l'Enseignement Supérieur et de la Recherche (MESRI) under reference APAFIS #20562-2019050313288887v3. Work with genetically modified mosquitoes was evaluated by Haut Conseil des Biotechnologies and authorized by MESRI (agréments d'utilisation d'OGM en milieu confiné #3243 and #3912).
Copyright
© 2023, Green et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A population modification gene drive targeting both Saglin and Lipophorin impairs Plasmodium transmission in Anopheles mosquitoes
eLife 12:e93142.
https://doi.org/10.7554/eLife.93142
Further reading
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