Sheltering DNA in self-organizing, protein-only nano-shells as artificial viruses for gene delivery

Ugutz Unzueta, Paolo Saccardo, Joan Domingo-Espín, Juan Cedano, Oscar Conchillo-Solé, Elena García-Fruitós, María Virtudes Céspedes, José Luis Corchero, Xavier Daura, Ramón Mangues, Neus Ferrer-Miralles, Antonio Villaverde, Esther Vázquez

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

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. © 2014 Elsevier Inc.
Original languageEnglish
Pages (from-to)535-541
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume10
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Artificial viruses
  • Gene therapy
  • Nanoparticles
  • Protein building blocks
  • Self-assembling

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