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


METHODS
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.


CONCLUSIONS
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.
McGill University, Artificial Cells and Organs Research Center, Departments of Biomedical Engineering and Physiology, Biomedical Technology and Cell Therapy Research Laboratory, Faculty of Medicine, 3775 University Street, Montreal, Quebec, H3A 2B4, Canada  +1 514 398 3676 ;  +1 514 398 7461 ;  satya.prakash@mcgill.ca.
Meenakshi
M
Malhotra
Shruti
S
Nambiar
Venkatesh
V
Rengaswamy
Satya
S
Prakash