Cationic nanosystems for the delivery of small interfering ribonucleic acid therapeutics: a focus on toxicogenomics

Areas covered in this review: A combination of highly focused and comprehensive literature searches to identify any relevant reports using Medline (from 1950 to 7 April 2010) through the OVID system. What the reader will gain: Using cationic delivery nanosystems as examples, this review article highlights the importance of undertaking toxicogenomics studies - the application of transcription profiling to toxicology - to acquire gene expression signatures of siRNA delivery systems so as to determine and/or predict their impact on gene silencing activity and specificity. Such nanotoxicological information will be important for the optimal selection of siRNA-delivery system combinations in the many proposed clinical applications of RNA interference. Take home message: Cationic delivery nanosystems can elicit multiple gene expression changes in cells that may contribute to the 'off-target' effects of siRNAs and/or modulate their pharmacological activity. Thus, selection of delivery systems for siRNA applications should be based on both their delivery enhancing capability and toxicogenomics.