Designing Dual-Targeting siRNA Duplexes Having Two Active Strands that Combine siRNA and MicroRNA-Like Targeting

Short interfering RNAs (siRNAs) have become valued tools for knocking down specific genes. As such, siRNAs are routinely used to study gene function and are also being explored as therapeutic agents. Traditionally, siRNAs are designed to target one specific gene, but this chapter describes a procedure for designing dual-targeting siRNAs where the two strands in the siRNA duplex are both active and down-regulate different target genes through both siRNA and miRNA-like effects. The procedure can be used to create siRNAs that robustly target pairs of genes.