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A synthetic sex ratio distortion system for the control of the human malaria mosquito.

Galizi, Roberto; Doyle, Lindsey A.; Menichelli, Miriam; Bernardini, Federica; Deredec, Anne; Burt, Austin; Stoddard, Barry L.; Windbichler, Nikolai; Crisanti, Andrea

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Authors

Lindsey A. Doyle

Miriam Menichelli

Federica Bernardini

Anne Deredec

Austin Burt

Barry L. Stoddard

Nikolai Windbichler

Andrea Crisanti



Abstract

It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action of naturally occurring sex distorters and the prevalence of co-evolving suppressors has hampered their use for control. Here we generate a synthetic sex distortion system by exploiting the specificity of the homing endonuclease I-PpoI, which is able to selectively cleave ribosomal gene sequences of the malaria vector Anopheles gambiae that are located exclusively on the mosquito's X chromosome. We combine structure-based protein engineering and molecular genetics to restrict the activity of the potentially toxic endonuclease to spermatogenesis. Shredding of the paternal X chromosome prevents it from being transmitted to the next generation, resulting in fully fertile mosquito strains that produce >95% male offspring. We demonstrate that distorter male mosquitoes can efficiently suppress caged wild-type mosquito populations, providing the foundation for a new class of genetic vector control strategies.

Journal Article Type Article
Acceptance Date Apr 28, 2014
Publication Date Jun 10, 2014
Publicly Available Date Mar 28, 2024
Journal Nature Communications
Print ISSN 2041-1723
Pages 3977 - ?
DOI https://doi.org/10.1038/ncomms4977
Keywords Malaria, mosquito.
Publisher URL https://www.nature.com/articles/ncomms4977
PMID 24915045

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