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Silencing or Stimulation? siRNA Delivery and the Immune System

Silencing or Stimulation? siRNA Delivery and the Immune System Since its inception more than a decade ago, the field of short interfering RNA (siRNA) therapeutics has demonstrated potential in the treatment of a wide variety of diseases. The power behind RNA interference (RNAi) therapy lies in its ability to specifically silence target genes of interest. As more biological data have become available, it has become evident that, in addition to mediating RNAi, siRNA molecules have the potential to potently induce the innate immune system. One of the significant challenges facing the field today is the differentiation between therapeutic effects caused by target-specific, RNAi-mediated gene silencing and those caused by nonspecific stimulation of the innate immune system. Unless appropriate experimental measures are taken to control for RNA-induced immunostimulation, genetic manipulation can be confused with immune activation. This review attempts to provide an accessible background in siRNA-relevant immunology and to highlight the ways in which siRNA can be engineered to avoid or provoke an innate immune response. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annual Review of Chemical and Biomolecular Engineering Annual Reviews

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Publisher
Annual Reviews
Copyright
Copyright © 2011 by Annual Reviews. All rights reserved
ISSN
1947-5438
eISSN
1947-5446
DOI
10.1146/annurev-chembioeng-061010-114133
pmid
22432611
Publisher site
See Article on Publisher Site

Abstract

Since its inception more than a decade ago, the field of short interfering RNA (siRNA) therapeutics has demonstrated potential in the treatment of a wide variety of diseases. The power behind RNA interference (RNAi) therapy lies in its ability to specifically silence target genes of interest. As more biological data have become available, it has become evident that, in addition to mediating RNAi, siRNA molecules have the potential to potently induce the innate immune system. One of the significant challenges facing the field today is the differentiation between therapeutic effects caused by target-specific, RNAi-mediated gene silencing and those caused by nonspecific stimulation of the innate immune system. Unless appropriate experimental measures are taken to control for RNA-induced immunostimulation, genetic manipulation can be confused with immune activation. This review attempts to provide an accessible background in siRNA-relevant immunology and to highlight the ways in which siRNA can be engineered to avoid or provoke an innate immune response.

Journal

Annual Review of Chemical and Biomolecular EngineeringAnnual Reviews

Published: Jul 15, 2011

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