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Transgenic Anopheles stephensi coexpressing single-chain antibodies resist Plasmodium falciparum development
Contributed by Anthony A. James, May 7, 2012 (sent for review January 28, 2012)

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.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: aajames{at}uci.edu.
Author contributions: A.T.I., N.J., I.T., A.Z., C.B., and A.A.J. designed research; A.T.I., N.J., M.T., I.T., A.Z., and C.B. performed research; A.T.I. contributed new reagents/analytic tools; A.T.I. and A.A.J. analyzed data; and A.T.I., C.B., and A.A.J. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1207738109/-/DCSupplemental.
Freely available online through the PNAS open access option.
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