Site-Specific Integration and Expression of an Anti-Malarial Gene in Transgenic Anopheles gambiae Significantly Reduces Plasmodium Infections

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dc.contributor.authorMeredith, Janet M.en
dc.contributor.authorBasu, Sanjayen
dc.contributor.authorNimmo, Derric D.en
dc.contributor.authorLarget-Thiery, Isabelleen
dc.contributor.authorWarr, Emma L.en
dc.contributor.authorUnderhill, Annen
dc.contributor.authorMcArthur, Clare C.en
dc.contributor.authorCarter, Victoriaen
dc.contributor.authorHurd, Hilaryen
dc.contributor.authorBourgouin, Catherineen
dc.contributor.authorEggleston, Paulen
dc.contributor.departmentEntomologyen
dc.date.accessioned2018-11-08T15:08:06Zen
dc.date.available2018-11-08T15:08:06Zen
dc.date.issued2011-01-25en
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
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0014587en
dc.identifier.eissn1932-6203en
dc.identifier.issue1en
dc.identifier.othere14587en
dc.identifier.pmid21283619en
dc.identifier.urihttp://hdl.handle.net/10919/85800en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleSite-Specific Integration and Expression of an Anti-Malarial Gene in Transgenic Anopheles gambiae Significantly Reduces Plasmodium Infectionsen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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