The AAPS Journal

, Volume 12, Issue 4, pp 492–503

Delivery of siRNA Therapeutics: Barriers and Carriers

Authors

    • Optimum Therapeutics LLCThe Ohio State University Science Tech Village
  • Ze Lu
    • Optimum Therapeutics LLCThe Ohio State University Science Tech Village
  • M. Guillaume Wientjes
    • Optimum Therapeutics LLCThe Ohio State University Science Tech Village
  • Jessie L.-S. Au
    • Optimum Therapeutics LLCThe Ohio State University Science Tech Village
Review Article Theme: siRNA and microRNA: From Target Validation to Therapy

DOI: 10.1208/s12248-010-9210-4

Cite this article as:
Wang, J., Lu, Z., Wientjes, M.G. et al. AAPS J (2010) 12: 492. doi:10.1208/s12248-010-9210-4

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 therapynanotechnologysiRNAsystemic deliveryvectors

Copyright information

© American Association of Pharmaceutical Scientists 2010