ABSTRACT
Short-interfering RNA (siRNA)—double-stranded RNA (dsRNA) with approximately 21 nt in length-is a powerful tool that has been widely used for downregulation of expression of speci„c genes.1-5 Introduction of siRNAs to mammalian cells leads to the sequence-speci„c destruction of endogenous mRNA molecules that are complementary to siRNAs (Figure 22.1). The cellular process that undergoes degradation of target mRNA via siRNA is termed RNA interference (RNAi). During RNAi, siRNAs appear to serve as guides for enzymatic cleavage of complementary RNAs. In addition, in some systems, siRNAs can function as primers for an RNA-dependent RNA polymerase that can synthesize additional siRNAs, which can enhance the effects of RNAi.1,4-8 Nevertheless, the mechanism by which complementary RNAs can be destroyed by siRNAs is not well understood, and the speci„c enzyme(s) that mediate siRNA functions remain to be identi„ed.
