His-tagged norovirus-like particles: A versatile platform for cellular delivery and surface display

Eur J Pharm Biopharm. 2015 Oct:96:22-31. doi: 10.1016/j.ejpb.2015.07.002. Epub 2015 Jul 10.

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.

Keywords: Bioconjugation; Cell entry peptide; Drug delivery; Molecular display; Targeting; Virus-like particle (VLP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotechnology / methods*
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Cell-Penetrating Peptides / chemistry
  • Drug Carriers / chemistry*
  • Epitopes / genetics
  • Epitopes / immunology
  • HEK293 Cells
  • Histidine / chemistry
  • Humans
  • Nitrilotriacetic Acid / chemistry
  • Norovirus / genetics
  • Norovirus / immunology*
  • Sf9 Cells
  • Technology, Pharmaceutical / methods
  • Vaccines, Virus-Like Particle / chemistry*
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology
  • Viral Vaccines* / administration & dosage
  • Viral Vaccines* / immunology

Substances

  • Capsid Proteins
  • Cell-Penetrating Peptides
  • Drug Carriers
  • Epitopes
  • Vaccines, Virus-Like Particle
  • Viral Vaccines
  • polyhistidine
  • Histidine
  • Nitrilotriacetic Acid