Meredith, JM and Basu, S and Nimmo, DD and Larget-Thiery, I and Warr, EL and Underhill, A and McArthur, CC and Carter, V and Hurd, H and Bourgouin, C and Eggleston, P (2011) Site-specific integration and expression of an anti-malarial gene in transgenic Anopheles gambiae significantly reduces Plasmodium infections. PLoS One, 6 (1). e14587 -?. ISSN 1932-6203

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Abstract

Diseases 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.

Item Type: Article
Uncontrolled Keywords: animals (genetically modified), anopheles gambiae, Antimalarials, gene targeting, female, humans, insect vectors, malaria, plasmodium falciparum, plasmodium yoelii, transgenes
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 09 Apr 2015 10:46
Last Modified: 30 Nov 2016 15:40
URI: http://eprints.keele.ac.uk/id/eprint/393

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