In silico selection of active siRNA

RNA interference (RNAi) mediated by short interfering RNA (siRNA) represents a powerful reverse genetics tool, and siRNAs are attracting increasing interest as potential therapeutics. Progress in the design of functional siRNAs has significantly contributed to our understanding of cellular RNA silencing pathways and vice versa. Parameters related to RNA sequence and structure have a strong impact on various steps along the silencing pathway and build the backbone of many siRNA design tools. Recent work has demonstrated that there is more to siRNA design than enhancement of gene silencing activity. Current efforts aim at avoidance of off-target effects, the understanding of siRNA-triggered immunostimulation, and evasion of interference with cellular regulatory RNA. Molecular features determining the biological functions of siRNA and their meaning for computational (in silico) selection are the focus of this review.