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

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.From the Clinical EditorFinding 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.

3D isosurface representation of internalized protein–DNA nanoparticles that are formed by green fluorescent building blocks and blue-labeled DNA. These artificial viruses, organized by means of synergistically acting end-terminal peptide tags, occur as rod-shaped entities in which the DNA core is shielded by a self-assembling, solvent-exposed protein shell. The red background corresponds to the cell membrane.Figure optionsDownload high-quality image (76 K)Download as PowerPoint slide