Overview of siRNA Delivery and Mechanisms: In-vitro and In-vivo Applications

siRNAs are RNA duplexes approximately 19-21 nucleotides  in length which in the context of endogenous eukaryotic proteins catalyze degradation of specific mRNAs in eukaryotic cells. The guide strand which is complementary to the targeted mRNA, incorporates into the RISC complex resulting in catalytic cleavage of  the complementary mRNA sequence leading to transient knock down of  protein expression. Using delivery vehicles to deliver siRNA into the cytosol of cells, siRNAs have been applied to study protein functions in vitro and in vivo.  The ability to design siRNAs targeting specific proteins based on known sequence as well as the potential to knock down gene expression in vivo makes RNAi a particularly attractive technique for evaluation of protein functions in cellular and physiological processes as well as a promising novel therapeutic modality. From a drug metabolism perspective the ability to knock down proteins in liver in vivo and in hepatocytes in vitro makes RNAi a particularly attractive technique for studying the impact of drug transporters and metabolism enzymes on drug pharmacokinetics.  This presentation will provide an introduction to RNAi and siRNA delivery in vivo.  Applications to knockdown of drug metabolism enzymes will be discussed.