oa Editorial [ Hot Topic:siRNA Based Approaches in Medicinal Chemistry and Drug Discovery (Guest Editor: Raymond M. Schiffelers )]

siRNAs can cleave complementary mRNAs. This ability to inhibit the translation of specific proteins offers important biomedical benefits from basic study of protein function through loss-of-function phenotypes up to therapeutic intervention in diseases resulting from expression of specific proteins [1]. When siRNA is considered as a drug molecule it has desirable and less attractive characteristics. One of the most appealing qualities is that, with the availability of the human genome sequence, siRNA design algorithms and oligonucleotide chemistry, interesting siRNA sequences can be readily identified and synthesized. This bypasses much of the need for lead compound identification and optimization that is a key process for traditional small molecular weight drugs. At the same time, siRNA molecules have very poor physicochemical characteristics to be drug molecules. Their nuclease sensitivity, molecular weight of approximately 14 kD and strong negative surface charge coupled to an intracellular site of activity make their application as drug molecules difficult [2]. In this special issue, we present a collection of papers that describe the possibilities of siRNA as a tool and of siRNA as a drug. Naturally, given the difficult physicochemical properties of the molecule itself, most attention in this section will be focused on the delivery. The paper of Zaffaroni and colleagues describes RNAi-based approaches to validate survivin and Apollon/BRUCE as new cancer therapeutic targets. It is an excellent example of the powerof siRNA as a tool in identification and functional characterization of new points for therapeutic intervention. Their results show that targeting the survivin pathway inhibits tumor growth by increasing apoptosis of cancer cells. Based on these findings, the clinical use of survivin-directed strategies is currently under investigation. Preliminary result on Apollon/BRUCE, indicate the induction of apoptosis in a similar manner, making this an interesting strategy for future exploration. The article by Ohrt et al. discusses the various pathways by which RNA can regulate gene expression and the intracellular location of this activity…..