title: SplitCore: an exceptionally versatile viral nanoparticle for native whole protein display regardless of 3D structure.
abstract: Nanoparticles displaying native proteins are attractive for many applications, including vaccinology. Virus-based nanoparticles are easily tailored by genetic means, commonly by inserting heterologous sequences into surface-exposed loops. The strategy works well with short peptides but is incompatible with the structures of most native proteins, except those with closely juxtaposed termini. Here we overcome this constraint by splitting the capsid protein of hepatitis B virus, one of the most advanced and most immunogenic display platforms, inside the insertion loop (SplitCore). The split parts, coreN and coreC, efficiently form capsid-like particles (CLPs) in E. coli and so do numerous fusions to coreN and/or coreC of differently structured proteins, including human disease related antigens of >300 amino acids in length. These CLPs induced high-titer antibodies, including neutralizing ones, in mice. The concept was easily expanded to triple-layer CLPs carrying reporter plus targeting domains, and should be applicable to protein-based nanoparticle design in general.
authors.affiliation: University Hospital Freiburg, Dept. of Internal Medicine II, Molecular Biology, D-79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, D-79104 Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Walker
authors.forename: Claudia
authors.initials: C
authors.lastname: Skamel
authors.forename: Michael
authors.initials: M
authors.lastname: Nassal
mesh_terms: D061505:Cell Surface Display Techniques / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D014771:Virion / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D011506:Proteins