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dc.contributor.authorMeredith, Janet M.en_US
dc.contributor.authorBasu, Sanjayen_US
dc.contributor.authorNimmo, Derric D.en_US
dc.contributor.authorLarget-Thiery, Isabelleen_US
dc.contributor.authorWarr, Emma L.en_US
dc.contributor.authorUnderhill, Annen_US
dc.contributor.authorMcArthur, Clare C.en_US
dc.contributor.authorCarter, Victoriaen_US
dc.contributor.authorHurd, Hilaryen_US
dc.contributor.authorBourgouin, Catherineen_US
dc.contributor.authorEggleston, Paulen_US
dc.date.accessioned2018-11-08T15:08:06Z
dc.date.available2018-11-08T15:08:06Z
dc.date.issued2011-01-25en_US
dc.identifier.othere14587en_US
dc.identifier.urihttp://hdl.handle.net/10919/85800
dc.description.abstractDiseases transmitted by mosquitoes have a devastating impact on global health and this is worsening due to difficulties with existing control measures and climate change. Genetically modified mosquitoes that are refractory to disease transmission are seen as having great potential in the delivery of novel control strategies. Historically the genetic modification of insects has relied upon transposable elements which have many limitations despite their successful use. To circumvent these limitations the Streptomyces phage phiC31 integrase system has been successfully adapted for site-specific transgene integration in insects. Here, we present the first site-specific transformation of Anopheles gambiae, the principal vector of human malaria. Mosquitoes were initially engineered to incorporate the phiC31 targeting site at a defined genomic location. A second phase of genetic modification then achieved site-specific integration of Vida3, a synthetic anti-malarial gene. Expression of Vida3, specifically in the midgut of bloodfed females, offered consistent and significant protection against Plasmodium yoelii nigeriensis, reducing average parasite intensity by 85%. Similar protection was observed against Plasmodium falciparum in some experiments, although protection was inconsistent. In the fight against malaria, it is imperative to establish a broad repertoire of both anti-malarial effector genes and tissue-specific promoters for their expression, enabling those offering maximum effect with minimum fitness cost to be identified. In the future, this technology will allow effective comparisons and informed choices to be made, potentially leading to complete transmission blockade.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.rightsCreative Commons Attribution 4.0 Internationalen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleSite-Specific Integration and Expression of an Anti-Malarial Gene in Transgenic Anopheles gambiae Significantly Reduces Plasmodium Infectionsen_US
dc.typeArticle - Refereeden_US
dc.description.versionPeer Revieweden_US
dc.title.serialPLOS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0014587en_US
dc.identifier.volume6en_US
dc.identifier.issue1en_US
dc.type.dcmitypeTexten_US
dc.identifier.pmid21283619en_US
dc.identifier.eissn1932-6203en_US


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Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International