Site-specific integration and expression of an anti-malarial gene in transgenic XXXX significantly reduces @entity3964 infections.

@entity27682 @entity1 @entity501 @entity3964 @entity311 @entity313
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 @entity27682 integrase system has been successfully adapted for site-specific transgene integration in insects. Here, we present the first site-specific transformation of @entity313 , the principal vector of @entity1 @entity311 . Mosquitoes were initially engineered to incorporate the @entity27682 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 @entity501 nigeriensis, reducing average parasite intensity by 85%. Similar protection was observed against @entity3964 in some experiments, although protection was inconsistent. In the fight against @entity311 , 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.
