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Transgenic Anopheles stephensi coexpressing single-chain antibodies resist Plasmodium falciparum development

Abstract : Anopheles stephensi mosquitoes expressing m1C3, m4B7, or m2A10 single-chain antibodies (scFvs) have significantly lower levels of infection compared to controls when challenged with Plasmodium falciparum, a human malaria pathogen. These scFvs are derived from antibodies specific to a parasite chitinase, the 25 kDa protein and the circumsporozoite protein, respectively. Transgenes comprising m2A10 in combination with either m1C3 or m4B7 were inserted into previously-characterized mosquito chromosomal "docking" sites using site-specific recombination. Transgene expression was evaluated at four different genomic locations and a docking site that permitted tissue- and sex-specific expression was researched further. Fitness studies of docking site and dual scFv transgene strains detected only one significant fitness cost: adult docking-site males displayed a late-onset reduction in survival. The m4B7/m2A10 mosquitoes challenged with P. falciparum had few or no sporozoites, the parasite stage infective to humans, in three of four experiments. No sporozoites were detected in m1C3/m2A10 mosquitoes in challenge experiments when both genes were induced at developmentally relevant times. These studies support the conclusion that expression of a single copy of a dual scFv transgene can completely inhibit parasite development without imposing a fitness cost on the mosquito.
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Submitted on : Thursday, April 23, 2020 - 2:34:08 PM
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Alison Isaacs, Nijole Jasinskiene, Mikhail Tretiakov, Isabelle Thiery, Agnes Zettor, et al.. Transgenic Anopheles stephensi coexpressing single-chain antibodies resist Plasmodium falciparum development. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2012, 109 (28), pp.E1922-E1930. ⟨10.1073/pnas.1207738109⟩. ⟨pasteur-02552282⟩

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