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Journal of Biomedicine and Biotechnology
Volume 2006, Article ID 23429, 4 pages
Review Article

Molecular Basis for the Immunostimulatory Potency of Small Interfering RNAs

Department of Immunology, Molecular Medicine Group, Institute for Cancer Research, Montebello 0310, Oslo, Norway

Received 5 March 2006; Revised 15 June 2006; Accepted 28 June 2006

Copyright © 2006 Mouldy Sioud and Gro Furset. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Small interfering RNAs (siRNAs) represent a new class of antigene agents, which has emerged as a powerful tool for functional genomics and might serve as a potent therapeutic approach. However, several studies have showed that they could trigger several bystander effects, including immune activation and inhibition of unintended target genes. Although activation of innate immunity by siRNAs might be beneficial for therapy in some instances, uncontrolled activation can be toxic, and is therefore a major challenging problem. Interestingly, replacement of uridines in siRNA sequences with their 2-modified counterparts abrogated siRNA bystander effects. Here we highlight these important findings that are expected to facilitate the rational design of siRNAs that avoid the induction of bystander effects.