Cell-penetrating peptides as versatile vehicles for oligonucleotide delivery

Mol Ther. 2012 Mar;20(3):525-33. doi: 10.1038/mt.2011.284. Epub 2012 Jan 10.

Abstract

Short regulatory oligonucleotides (ONs) have a great therapeutic potential for the modulation of gene expression due to their high specificity and low toxicity. The major obstacles for in vivo clinical applications of ONs are the poor permeability of plasma membrane to nucleic acids and the sensitivity of ONs to enzymatic degradation. Hence, various delivery vehicles have been developed to ensure the transduction of ONs into cells. Among these, the cell-penetrating peptides (CPPs) have gained quickly broadening popularity as promising nonviral transmembrane delivery vectors. For coupling of nucleic acids to CPPs, two distinct strategies may be applied-covalent and noncovalent. The majority of earlier studies have used covalent coupling of CPPs to ONs. However, the number of studies demonstrating very high therapeutic potential of noncovalent complexes of ONs with novel CPP-based delivery vehicles is explosively increasing. In this review, the recent developments in the application of CPP-mediated oligonucleotide delivery by noncovalent strategy will be discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell-Penetrating Peptides / chemistry*
  • Cell-Penetrating Peptides / metabolism
  • Drug Delivery Systems*
  • Gene Transfer Techniques
  • Humans
  • Oligonucleotides, Antisense / administration & dosage*
  • Oligonucleotides, Antisense / chemistry
  • Oligonucleotides, Antisense / metabolism
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / metabolism

Substances

  • Cell-Penetrating Peptides
  • Oligonucleotides, Antisense
  • RNA, Small Interfering