Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms4977
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Funding
- Foundation for the National Institutes of Health through the Vector-Based Control of Transmission: Discovery Research (VCTR) programme of the Grand Challenges in Global Health initiative of the Bill & Melinda Gates Foundation
- European Research Council under the European Union's Seventh Framework Programme ERC grant [335724]
- European Commission
- Regione Umbria [I-MOVE-PCOFUND-GA-2010-267332]
- European Research Council (ERC) [335724] Funding Source: European Research Council (ERC)
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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.
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