1. Mechanisms and Barriers to RNAi Delivery

  1. Kun Cheng2 and
  2. Ram I. Mahato3
  1. Jiehua Zhou and
  2. John J. Rossi

Published Online: 26 APR 2013

DOI: 10.1002/9781118610749.ch1

Advanced Delivery and Therapeutic Applications of RNAi

Advanced Delivery and Therapeutic Applications of RNAi

How to Cite

Zhou, J. and Rossi, J. J. (2013) Mechanisms and Barriers to RNAi Delivery, in Advanced Delivery and Therapeutic Applications of RNAi (eds K. Cheng and R. I. Mahato), John Wiley and Sons, Ltd, Chichester, UK. doi: 10.1002/9781118610749.ch1

Editor Information

  1. 2

    School of Pharmacy, University of Missouri-Kansas City, USA

  2. 3

    Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, USA

Author Information

  1. Molecular and Cellular Biology, Beckman Research Institute of City of Hope, USA

Publication History

  1. Published Online: 26 APR 2013
  2. Published Print: 10 JUN 2013

ISBN Information

Print ISBN: 9781119976868

Online ISBN: 9781118610749

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Keywords:

  • RNA interference (RNAi);
  • small interfering RNA (siRNA);
  • targeted delivery;
  • nanocarrier;
  • passive targeting;
  • active targeting

Summary

RNA interference (RNAi) is an evolutionarily conserved, endogenous process for post-transcriptional regulation of gene expression. By taking advantage of the cell's RNAi machinery small interfering RNA (siRNA) duplexes of 21–25 nt in length can be introduced into cells to induce the specific degradation of targeted mRNAs. With the specificity and high efficacy of RNAi, the prospects of using siRNAs for treating human malignancies and other diseases remain tantalizing, but are still not fully realized due to several key barriers, such as inefficient delivery to the correct cells or tissues; suboptimal gene-silencing activity owing to instability and unavailability of the RNAi agents; systemic toxicity due to off-target effects or innate immune activation. Recent setbacks in RNAi clinical translation have stimulated further investigation into the molecular mechanism of RNAi as well as safe and efficient delivery formulations for achieving clinically relevant post-transcriptional gene silencing in the desired target tissue. In this chapter, we discuss the mechanisms of RNAi and the major barriers in achieving efficient RNAi delivery, particularly emphasizing recent advances addressing these challenges.