title: Engineered resistance to Plasmodium falciparum development in transgenic Anopheles stephensi.
abstract: Transposon-mediated transformation was used to produce Anopheles stephensi that express single-chain antibodies (scFvs) designed to target the human malaria parasite, Plasmodium falciparum. The scFvs, m1C3, m4B7, and m2A10, are derived from mouse monoclonal antibodies that inhibit either ookinete invasion of the midgut or sporozoite invasion of salivary glands. The scFvs that target the parasite surface, m4B7 and m2A10, were fused to an Anopheles gambiae antimicrobial peptide, Cecropin A. Previously-characterized Anopheles cis-acting DNA regulatory elements were included in the transgenes to coordinate scFv production with parasite development. Gene amplification and immunoblot analyses showed promoter-specific increases in transgene expression in blood-fed females. Transgenic mosquito lines expressing each of the scFv genes had significantly lower infection levels than controls when challenged with P. falciparum.
authors.affiliation: Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, California, United States of America.
authors.forename: Alison T
authors.initials: AT
authors.lastname: Isaacs
authors.forename: Fengwu
authors.initials: F
authors.lastname: Li
authors.forename: Nijole
authors.initials: N
authors.lastname: Jasinskiene
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
authors.forename: Xavier
authors.initials: X
authors.lastname: Nirmala
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Marinotti
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Vinetz
authors.forename: Anthony A
authors.initials: AA
authors.lastname: James
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D030781:Organisms, Genetically Modified / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D057127:Single-Chain Antibodies / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D019076:Transgenes / Q000502:physiology
chemical_list: D057127:Single-Chain Antibodies