RNAi through short interfering RNA (siRNAs) as a Novel Therapeutic Strategy

摘要

Since RNA interference (RNAi) was discovered in the late 1990s, it has evolved as a powerful and widely used strategy for the efficient silencing of genes. RNAi relies on the action of small interfering RNAs (siRNAs) which are incorporated into a complex termed RNA-induced silencing complex (RISC) and guide RISC to its cleavage site on the target mRNA. Thus, the efficiency of RNAi in vitro and in vivo is determined by the efficacy and intracellular presence of specific siRNA molecules. In vivo, the delivery of siRNAs is a major obstacle in the development of RNAi-based strategies also for clinical applications. Various approaches have been explored for the administration of RNAi in different pathological disorders. This review highlights criteria for the development of optimal siRNAs as well as strategies for siRNA stabilization and in vivo delivery. Different routes of siRNA administration and various siRNA formulations are discussed. The second part of the review provides a comprehensive overviewon siRNA-mediated in vivo gene targeting in proof-of-principle studies as well as for the treatment of various pathologies including e.g. viral infection, cancer, liver and renal failure, CNS disorders and pathological ocular neovascularization.