Figure 1.

A) Structure of an siRNA. The two strands of the siRNA form an approximately 19 nucleotide duplex. Two nucleotides hang over from each 3′ end. Deoxythymidine is often used as the overhangs in chemically synthesized siRNAs. The position at which the complementary target RNA is cleaved is indicated with an arrow, and the seed region, through which the interaction with the target RNA begins, is indicated. B) Simplified model of the RNAi mechanism in mammalian cells. After uptake of the chemically synthesized siRNAs into the cells, they are loaded onto the RISC by the RLC, in the course of which the sense strand is removed. The antisense strand guides the RISC to the complementary target RNA, which is cleaved by the Ago2 protein. A longer term inhibition of gene expression can be accomplished when an shRNA is expressed intracellularly instead of by the exogenous application of an siRNA. (Figure adapted from Ref. 9.)