Development of a microRNA delivery system based on bacteriophage MS2 virus-like particles

FEBS J. 2012 Apr;279(7):1198-208. doi: 10.1111/j.1742-4658.2012.08512.x. Epub 2012 Feb 23.

Abstract

Recently, microRNA (miRNA)-mediated RNA interference has been developed as a useful tool in gene function analysis and gene therapy. A major obstacle in miRNA-mediated RNAi is cellular delivery, which requires an efficient and flexible delivery system. The self-assembly of the MS2 bacteriophage capsids has been used to develop virus-like particles (VLPs) for RNA and drug delivery. However, MS2 VLP-mediated miRNA delivery has not yet been reported. We therefore used an Escherichia coli expression system to produce the pre-miR 146a contained MS2 VLPs, and then conjugated these particles with HIV-1 Tat(47-57) peptide. The conjugated MS2 VLPs effectively transferred the packaged pre-miR146a RNA into various cells and tissues, with 0.92-14.76-fold higher expression of miR-146a in vitro and about two-fold higher expression in vivo, and subsequently suppressed its targeting gene. These findings suggest that MS2 VLPs can be used as a novel vehicle in miRNA delivery systems, and may have applications in gene therapy.

MeSH terms

  • Animals
  • Cell Line
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Humans
  • Levivirus / genetics
  • Levivirus / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • RNA Interference
  • Virion / metabolism*
  • Virion / ultrastructure
  • tat Gene Products, Human Immunodeficiency Virus / genetics
  • tat Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • MicroRNAs
  • Peptide Fragments
  • tat Gene Products, Human Immunodeficiency Virus
  • tat peptide (47-57), Human immunodeficiency virus 1