title: Multivalent display of proteins on viral nanoparticles using molecular recognition and chemical ligation strategies.
abstract: Multivalent display of heterologous proteins on viral nanoparticles forms a basis for numerous applications in nanotechnology, including vaccine development, targeted therapeutic delivery, and tissue-specific bioimaging. In many instances, precise placement of proteins is required for optimal functioning of the supramolecular assemblies, but orientation- and site-specific coupling of proteins to viral scaffolds remains a significant technical challenge. We have developed two strategies that allow for controlled attachment of a variety of proteins on viral particles using covalent and noncovalent principles. In one strategy, an interaction between domain 4 of anthrax protective antigen and its receptor was used to display multiple copies of a target protein on virus-like particles. In the other, expressed protein ligation and aniline-catalyzed oximation was used to display covalently a model protein. The latter strategy, in particular, yielded nanoparticles that induced potent immune responses to the coupled protein, suggesting potential applications in vaccine development.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: P Arno
authors.initials: PA
authors.lastname: Venter
authors.forename: Anouk
authors.initials: A
authors.lastname: Dirksen
authors.forename: Diane
authors.initials: D
authors.lastname: Thomas
authors.forename: Marianne
authors.initials: M
authors.lastname: Manchester
authors.forename: Philip E
authors.initials: PE
authors.lastname: Dawson
authors.forename: Anette
authors.initials: A
authors.lastname: Schneemann
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry*; D001427:Bacterial Toxins / Q000737:chemistry*; D016367:Baculoviridae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D003001:Cloning, Molecular; D004926:Escherichia coli; D058619:Maltose-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D049329:Nanostructures / Q000737:chemistry* / Q000821:virology; D036103:Nanotechnology / Q000379:methods*; D010091:Oximes / Q000737:chemistry; D010957:Plasmids; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera; D013237:Stereoisomerism; D020349:Surface Plasmon Resonance; D014162:Transfection; D014771:Virion / Q000235:genetics / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D058619:Maltose-Binding Proteins; D010091:Oximes; D011994:Recombinant Proteins; C030325:anthrax toxin; C023650:aniline