Review Article Theme: siRNA and microRNA: From Target Validation to Therapy

The AAPS Journal

, Volume 12, Issue 4, pp 492-503

First online:

Delivery of siRNA Therapeutics: Barriers and Carriers

  • Jie WangAffiliated withOptimum Therapeutics LLC, The Ohio State University Science Tech Village Email author 
  • , Ze LuAffiliated withOptimum Therapeutics LLC, The Ohio State University Science Tech Village
  • , M. Guillaume WientjesAffiliated withOptimum Therapeutics LLC, The Ohio State University Science Tech Village
  • , Jessie L.-S. AuAffiliated withOptimum Therapeutics LLC, The Ohio State University Science Tech Village

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Abstract

RNA interference is a naturally occurring endogenous regulatory process where short double-stranded RNA causes sequence-specific posttranscriptional gene silencing. Small interference RNA (siRNA) represents a promising therapeutic strategy. Clinical evaluations of siRNA therapeutics in locoregional treatment settings began in 2004. Systemic siRNA therapy is hampered by the barriers for siRNA to reach their intended targets in the cytoplasm and to exert their gene silencing activity. The three goals of this review were to provide an overview of (a) the barriers to siRNA delivery, from the perspectives of physicochemical properties of siRNA, pharmacokinetics and biodistribution, and intracellular trafficking; (b) the non-viral siRNA carriers including cell-penetrating peptides, polymers, dendrimers, siRNA bioconjugates, and lipid-based siRNA carriers; and (c) the current status of the clinical trials of siRNA therapeutics.

Key words

gene therapy nanotechnology siRNA systemic delivery vectors