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.