Introduction

A major challenge in the post genomic era of biology is to decipher the molecular function of over 30,000 genes. The gene knock-out by homologous recombination has proven to be very useful but is laborious and expensive. RNA interference has recently emerged as a novel pathway that allows modulation of gene expression. The basic biology of RNAi is described in the next section. Briefly, long dsRNA molecules are processed by the endonuclease Dicer into short 21–23 nucleotide small interfering RNAs (siRNAs), which are then incorporated into RISC (RNA-induced silencing complex), a multi-component nuclease complex that selects and degrades mRNAs that are homolgous to the dsRNA initially delivered (Fjose et al., 2001; Hannon, 2002). In mammalian systems, synthetic siRNA's can be delivered exogenously (Elbashir et al., 2001) or can be expressed endogenously from RNA Pol III promoters, resulting in a powerful tool for achieving specific downregulation of target mRNA's (Miyagashi and Taira, 2002; Paul et al., 2002; Oliviera and Goodell, 2003). The delivery of synthetic siRNAs to cells in culture is hampered by limitations in transfection efficiency for many cell types and the transient nature of the silencing effect. In vivo, delivering siRNAs to target cells is difficult due to lack of stability of siRNA and low uptake efficiency in the absence of transfection agents (Isacson et al., 2003). Thus in order to apply this potent technique to both basic biological questions and therapeutic strategies, efficient siRNA delivery methods must be developed.