Engineered Resistance to Plasmodium Falciparum Development in Transgenic Anopheles Stephensi

PLoS Pathog. 2011 Apr;7(4):e1002017. doi: 10.1371/journal.ppat.1002017. Epub 2011 Apr 21.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles / genetics
  • Anopheles / immunology
  • Anopheles / metabolism*
  • Female
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Organ Specificity / genetics
  • Organ Specificity / immunology
  • Organisms, Genetically Modified / genetics
  • Organisms, Genetically Modified / immunology
  • Organisms, Genetically Modified / metabolism*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology
  • Plasmodium falciparum / metabolism*
  • Promoter Regions, Genetic / physiology
  • Salivary Glands / immunology
  • Salivary Glands / metabolism*
  • Salivary Glands / physiology
  • Single-Chain Antibodies / biosynthesis*
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology
  • Transgenes / physiology

Substances

  • Single-Chain Antibodies