Progress in microRNA delivery

J Control Release. 2013 Dec 28;172(3):962-74. doi: 10.1016/j.jconrel.2013.09.015. Epub 2013 Sep 25.


MicroRNAs (miRNAs) are non-coding endogenous RNAs that direct post-transcriptional regulation of gene expression by several mechanisms. Activity is primarily through binding to the 3' untranslated regions (UTRs) of messenger RNAs (mRNA) resulting in degradation and translation repression. Unlike other small-RNAs, miRNAs do not require perfect base pairing, and thus, can regulate a network of broad, yet specific, genes. Although we have only just begun to gain insights into the full range of biologic functions of miRNA, their involvement in the onset and progression of disease has generated significant interest for therapeutic development. Mounting evidence suggests that miRNA-based therapies, either restoring or repressing miRNAs expression and activity, hold great promise. However, despite the early promise and exciting potential, critical hurdles often involving delivery of miRNA-targeting agents remain to be overcome before transition to clinical applications. Limitations that may be overcome by delivery include, but are not limited to, poor in vivo stability, inappropriate biodistribution, disruption and saturation of endogenous RNA machinery, and untoward side effects. Both viral vectors and nonviral delivery systems can be developed to circumvent these challenges. Viral vectors are efficient delivery agents but toxicity and immunogenicity limit their clinical usage. Herein, we review the recent advances in the mechanisms and strategies of nonviral miRNA delivery systems and provide a perspective on the future of miRNA-based therapeutics.

Keywords: 1,2-Di-O-octadecenyl-3-trimethylammonium propane; 2′-MOE; 2′-Me; 2′-methoxyethyl; 2′-methyl; AMO; APP; BBB; CNS; CSC; DDAB; DGCR8; DNA; DOTMA; DiGeorge syndrome critical region gene; FANA; GC4; HCV; Human disease; IR; LAC; LNA; LPH; MicroRNA; NLE; NSCLC; Nonviral delivery; ODN; PEI; PNA; PU; RISC; RNA; RNA induced silencing complex: scFv, single-chain variable fragment; Small RNA delivery; TEPA-PCL; TPGS; UTR; VEGF; amyloid precursor protein; anti-miRNA oligonucleotides; base pairs; blood–brain barrier; bp; cancer stem cell; central nervous system; d-alpha-tocopheryl polyethylene glycol 1000 succinate; deoxyribonucleic acid; dicetyl phosphate-tetraethylenepentamine-based polycation liposomes; dimethyldioctadecylammonium bromide; fluorine derivatives nucleic acid; hepatitis C virus; iNOP; ionizing radiation; liposome-hyaluronic acid; locked nucleic acid; lung adenocarcinoma; miRNA; miRNA therapeutics; microRNA; nanotransporter interfering nanoparticle-7; neutral lipid emulsion; non-small cell lung cancer; nt; nucleotides; oligodeoxynucleotides; peptide nucleic acids; phage identified internalizing scFvs that target tumor sphere cells; polyethyleneimine; polyurethane; ribonucleic acid; siRNA; small interfering RNA; untranslated regions; vascular endothelial growth factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dendrimers / chemistry
  • Drug Delivery Systems* / methods
  • Gene Expression Regulation
  • Gene Transfer Techniques*
  • Humans
  • Lactic Acid / chemistry
  • Lipids / chemistry
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics
  • MicroRNAs / pharmacokinetics
  • MicroRNAs / therapeutic use*
  • Polyethyleneimine / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Tissue Distribution


  • Dendrimers
  • Lipids
  • MicroRNAs
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Polyethyleneimine