Journal
NUCLEIC ACIDS RESEARCH
Volume 35, Issue 17, Pages 5922-5933Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkm632
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Funding
- Medical Research Council [G0600062] Funding Source: Medline
- MRC [G0600062] Funding Source: UKRI
- NERC [cpb010001] Funding Source: UKRI
- Medical Research Council [G0600062] Funding Source: researchfish
- Natural Environment Research Council [cpb010001] Funding Source: researchfish
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Homing endonuclease genes (HEGs) are selfish genetic elements that combine the capability to selectively disrupt specific gene sequences with the ability to rapidly spread from a few individuals to an entire population through homologous recombination repair events. Because of these properties, HEGs are regarded as promising candidates to transfer genetic modifications from engineered laboratory mosquitoes to wild-type populations including Anopheles gambiae the vector of human malaria. Here we show that I-SceI and I-PpoI homing endonucleases cleave their recognition sites with high efficiency inA. gambiae cells and embryos and we demonstrate HEG-induced homologous and non-homologous repair events in a variety of functional assays. We also propose a gene drive system for mosquitoes that is based on our finding that I-PpoI cuts genomic rDNA located on the X chromosome in A. gambiae, which could be used to selectively incapacitate X-carrying spermatozoa thereby imposing a severe male-biased sex ratio.
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