Introduction

RNA interference (RNAi) was discovered in the worm C. elegans as an endogenous, double-stranded RNA (dsRNA) driven mechanism resulting in a specific inhibition of gene expression on a posttranscriptional level (Fire et al., 1998). Since then, gene suppression by RNA interference has been widely applied to study gene function in a variety of organisms (Hannon, 2002). Double-stranded small interfering RNA (siRNA) of 21 to 23 nucleotides was identified as mediator of this silencing signal in a Drosophila embryo lysate system (Elbashir et al., 2001b). In a seminal study it was demonstrated that exogenously delivered chemically synthesized siRNA can function as trigger for this specific silencing mechanism in mammalian cells (Elbashir et al., 2001a). Initial experiments indicated that, in contrast to long dsRNA, siRNA does not stimulate an unspecific inhibition of protein synthesis mediated by activation of protein kinase R (PKR) in mammals (Caplen et al., 2001). Because of its specificity and high efficiency as well as simple practicability, siRNA triggered RNAi has become rapidly accepted as the method of choice for studying gene function in cell culture systems. Moreover, recent reports demonstrated the successful siRNA-mediated down-regulation of reporter genes (McCaffrey et al., 2002; Lewis et al., 2002) as well as endogenous target genes in mice (Xia et al., 2002; Song et al., 2003; Rubinson et al., 2003). Now, researchers in academia and industry are attempting to utilize RNAi as a platform for the development of therapeutics.