title: His-tagged norovirus-like particles: A versatile platform for cellular delivery and surface display.
abstract: In addition to vaccines, noninfectious virus-like particles (VLPs) that mimic the viral capsid show an attractive possibility of presenting immunogenic epitopes or targeting molecules on their surface. Here, functionalization of norovirus-derived VLPs by simple non-covalent conjugation of various molecules is shown. By using the affinity between a surface-exposed polyhistidine-tag and multivalent tris-nitrilotriacetic acid (trisNTA), fluorescent dye molecules and streptavidin-biotin conjugated to trisNTA are displayed on the VLPs to demonstrate the use of these VLPs as easily modifiable nanocarriers as well as a versatile vaccine platform. The VLPs are able to enter and deliver surface-displayed fluorescent dye into HEK293T cells via a surface-attached cell internalization peptide (VSV-G). The ease of manufacturing, the robust structure of these VLPs, and the straightforward conjugation provide a technology, which can be adapted to various applications in biomedicine.
authors.affiliation: BioMediTech, University of Tampere, Biokatu 6, FI-33520 Tampere, Finland.
authors.forename: Tiia
authors.initials: T
authors.lastname: Koho
authors.affiliation: BioMediTech, University of Tampere, Biokatu 6, FI-33520 Tampere, Finland.
authors.forename: Teemu O
authors.initials: TO
authors.lastname: Ihalainen
authors.affiliation: Department of Biological and Environmental Science/Nanoscience Center, Survontie 9, FI-40500 Jyväskylä, Finland.
authors.forename: Marie
authors.initials: M
authors.lastname: Stark
authors.affiliation: Vaccine Research Center, Medical School, University of Tampere, Biokatu 10, FI-33520 Tampere, Finland.
authors.forename: Hanni
authors.initials: H
authors.lastname: Uusi-Kerttula
authors.affiliation: Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Wieneke
authors.affiliation: BioMediTech, University of Tampere, Biokatu 6, FI-33520 Tampere, Finland.
authors.forename: Rolle
authors.initials: R
authors.lastname: Rahikainen
authors.affiliation: Vaccine Research Center, Medical School, University of Tampere, Biokatu 10, FI-33520 Tampere, Finland.
authors.forename: Vesna
authors.initials: V
authors.lastname: Blazevic
authors.affiliation: Department of Biological and Environmental Science/Nanoscience Center, Survontie 9, FI-40500 Jyväskylä, Finland.
authors.forename: Varpu
authors.initials: V
authors.lastname: Marjomäki
authors.affiliation: Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Tampé
authors.affiliation: BioMediTech, University of Tampere, Biokatu 6, FI-33520 Tampere, Finland.
authors.forename: Markku S
authors.initials: MS
authors.lastname: Kulomaa
authors.affiliation: BioMediTech, University of Tampere, Biokatu 6, FI-33520 Tampere, Finland; Fimlab Laboratories, Biokatu 4, FI-33520 Tampere, Finland. Electronic address: Vesa.Hytonen@uta.fi.
authors.forename: Vesa P
authors.initials: VP
authors.lastname: Hytönen
mesh_terms: D000818:Animals; D001709:Biotechnology / Q000379:methods*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D006639:Histidine / Q000737:chemistry; D006801:Humans; D009571:Nitrilotriacetic Acid / Q000737:chemistry; D029322:Norovirus / Q000235:genetics / Q000276:immunology*; D061987:Sf9 Cells; D013678:Technology, Pharmaceutical / Q000379:methods; D058425:Vaccines, Virus-Like Particle / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D000939:Epitopes; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines; C033223:polyhistidine; D006639:Histidine; D009571:Nitrilotriacetic Acid
keywords: Bioconjugation; Cell entry peptide; Drug delivery; Molecular display; Targeting; Virus-like particle (VLP)