Small interfering ribonucleic acid design strategies for effective targeting and gene silencing

Abstract

Introduction: Gene silencing mediated by siRNAs is becoming a promising therapeutic approach. Although many strategies and technologies have been applied to siRNA design, a key issue lies in the selection of efficient design predictors. Furthermore, the development of systemic siRNA delivery strategies, which would enhance the therapeutic effect, remains a central issue.

Areas covered: The review discusses the basic principles of the sequence-specific design criteria of functional siRNAs and possible chemical modifications. Some of the most recent advances in the development of siRNA design algorithms and delivery strategies are also presented. Emphasis is given to the important design rule sets and predictors which determine the functionality of an efficient siRNA.

Expert opinion: The potential and limitations of efficient design predictors obtained from computational algorithms play a crucial role in the development of target-specific siRNAs. Furthermore, the future success of RNA interference therapeutics will depend on their ability to efficiently cross the physiological barriers, selectively target cells-of-interest and finally silence the gene-of-interest without any side effects.

Keywords::

• efficient delivery
• gene silencing
• off-target effect
• RNA interference
• siRNA chemical modifications siRNA delivery
• siRNA design algorithms
• siRNA design rules

Acknowledgements

The authors would like to thank the peer reviewers for their critical comments and constructive suggestions, and C Tomaro-Duchesneau for proof reading the article. The permission to use the concepts of Dr Ui-Tei to make Figure 3 is kindly acknowledged.

Notes

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