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Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):E1922-30. doi: 10.1073/pnas.1207738109. Epub 2012 Jun 11.

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

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1
Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697-4500, USA.

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.

PMID:
22689959
PMCID:
PMC3396534
DOI:
10.1073/pnas.1207738109
[Indexed for MEDLINE]
Free PMC Article
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