Nanoparticulate architecture of protein-based artificial viruses is supported by protein-DNA interactions

Joan Domingo-Espín, Esther Vazquez, Javier Ganz, Oscar Conchillo, Elena García-Fruitós, Juan Cedano, Ugutz Unzueta, Valérie Petegnief, Nuria Gonzalez-Montalbán, Anna M. Planas, Xavier Daura, Hugo Peluffo, Neus Ferrer-Miralles, Antonio Villaverde*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

Aim & Methods: We have produced two chimerical peptides of 10.2 kDa, each contain four biologically active domains, which act as building blocks of protein-based nonviral vehicles for gene therapy. In solution, these peptides tend to aggregate as amorphous clusters of more than 1000 nm, while the presence of DNA promotes their architectonic reorganization as mechanically stable nanometric spherical entities of approximately 80 nm that penetrate mammalian cells through arginine-glycine-aspartic acid cell-binding domains and promote significant transgene expression levels. Results & Conclusion: The structural analysis of the protein in these hybrid nanoparticles indicates a molecular conformation with predominance of α-helix and the absence of cross-molecular, β-sheet-supported protein interactions. The nanoscale organizing forces generated by DNA-protein interactions can then be observed as a potentially tunable, critical factor in the design of protein-only based artificial viruses for gene therapy.

Original languageAmerican English
Pages (from-to)1047-1061
Number of pages15
JournalNanomedicine
Volume6
Issue number6
DOIs
Publication statusPublished - Aug 2011

Keywords

  • DNA-protein interaction
  • gene therapy
  • innovative medicine
  • nanomedicine
  • protein engineering
  • protein nanoparticl

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