Introduction

Novel tools for evaluating gene function in vivo such as ribozymes and RNA interference (RNAi) are emerging as the most highly effective strategies (Sioud, 2001; Sioud, 2004; Hannon, 2002). RNAi is sequence-specific posttranscriptional gene silencing, which is triggered by double stranded RNA (dsRNA). This evolutionally conserved gene-silencing pathway triggered by dsRNAs was first described in the nematode worm Caenorhabditis elegans (Fire et al., 1998). This process has been linked to many previously described phenomena such as post-transcriptional gene silencing (PTGS) in plants (Jorgensen, 1990). The difficulty of using RNAi in somatic mammalian cells was overcome when Tuschl and colleagues discovered that siRNAs (21 nt), normally generated from long dsRNA during RNAi, could be used to inhibit specific gene targets (Elbashir et al., 2001). Currently, there is a great interest in the use of small interfering RNA as a research tool to study gene function and drug target validation (Dykxhoorn et al., 2003; Sørensen et al., 2003).

The therapeutic application of siRNAs, however, is largely dependent on the development of a delivery vehicle that can efficiently deliver the siRNAs to target cells. In addition, such delivery vehicles should be administered efficiently, safely and repeatedly. Cationic liposomes represent one of the few examples that can meet these requirements (Templeton, 2002). These agents are composed of positively charged lipid bilayers, and can be complexed to negatively charged siRNA duplexes. The routes of delivery include direct injection (e.g. intratumoral), intravenous, intraperitoneal, intraarterial, intracranial, and others.