title: Sheltering DNA in self-organizing, protein-only nano-shells as artificial viruses for gene delivery.
abstract: By recruiting functional domains supporting DNA condensation, cell binding, internalization, endosomal escape and nuclear transport, modular single-chain polypeptides can be tailored to associate with cargo DNA for cell-targeted gene therapy. Recently, an emerging architectonic principle at the nanoscale has permitted tagging protein monomers for self-organization as protein-only nanoparticles. We have studied here the accommodation of plasmid DNA into protein nanoparticles assembled with the synergistic assistance of end terminal poly-arginines (R9) and poly-histidines (H6). Data indicate a virus-like organization of the complexes, in which a DNA core is surrounded by a solvent-exposed protein layer. This finding validates end-terminal cationic peptides as pleiotropic tags in protein building blocks for the mimicry of viral architecture in artificial viruses, representing a promising alternative to the conventional use of viruses and virus-like particles for nanomedicine and gene therapy.
  
  
  BACKGROUND
  Finding efficient gene delivery methods still represents a challenge and is one of the bottlenecks to the more widespread application of gene therapy. The findings presented in this paper validate the application of end-terminal cationic peptides as pleiotropic tags in protein building blocks for "viral architecture mimicking" in artificial viruses, representing a promising alternative to the use of viruses and virus-like particles for gene delivery.
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Ugutz
authors.initials: U
authors.lastname: Unzueta
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Paolo
authors.initials: P
authors.lastname: Saccardo
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Domingo-Espín
authors.affiliation: Laboratory of Immunology, Regional Norte, Universidad de la República,, Salto, Uruguay.
authors.forename: Juan
authors.initials: J
authors.lastname: Cedano
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Conchillo-Solé
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Fruitós
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain; Grup d'Oncogènesi i Antitumorals, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: María Virtudes
authors.initials: MV
authors.lastname: Céspedes
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Corchero
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Daura
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain; Grup d'Oncogènesi i Antitumorals, Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Mangues
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Ferrer-Miralles
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain. Electronic address: antoni.villaverde@uab.cat.
authors.forename: Antonio
authors.initials: A
authors.lastname: Villaverde
authors.affiliation: Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, Barcelona, Spain. Electronic address: esther.vazquez@uab.cat.
authors.forename: Esther
authors.initials: E
authors.lastname: Vázquez
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006367:HeLa Cells; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*
chemical_list: D010455:Peptides; D011506:Proteins; C015462:polyarginine; C033223:polyhistidine; D006639:Histidine; D004247:DNA
keywords: Artificial viruses; Gene therapy; Nanoparticles; Protein building blocks; Self-assembling