Polymer nanoparticle-mediated delivery of microRNA inhibition and alternative splicing

Mol Pharm. 2012 May 7;9(5):1481-8. doi: 10.1021/mp300081s. Epub 2012 Apr 18.


The crux of current RNA-based therapeutics relies on association of synthetic nucleic acids with cellular RNA targets. Antisense oligonucleotide binding to mature microRNA and splicing junctions on pre-mRNA represent methods of gene therapy that respectively inhibit microRNA-mediated gene regulation and induce alternative splicing. We have developed biodegradable polymer nanoparticles, which are coated with cell-penetrating peptides, that can effectively deliver chemically modified oligonucleotide analogues to achieve these forms of gene regulation. We found that this nanoparticle system could block the activity of the oncogenic microRNA, miR-155, as well as modulate splicing to attenuate the expression of the proto-oncogene, Mcl-1. Regulation of these genes in human cancer cells reduced cell viability and produced pro-apoptotic effects. These findings establish polymer nanoparticles as delivery vectors for nonconventional forms of gene therapy activated by cellular delivery of RNA-targeted molecules, which have strong therapeutic implications.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alternative Splicing / genetics*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Humans
  • MicroRNAs / genetics*
  • Morpholines
  • Nanoparticles / chemistry*
  • Peptide Nucleic Acids
  • Polymers / chemistry*
  • Reverse Transcriptase Polymerase Chain Reaction


  • MicroRNAs
  • Morpholines
  • Peptide Nucleic Acids
  • Polymers