Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo

[摘要] RNA interference (RNAi) is a powerful method for specific genesilencing which may also lead to promising novel therapeuticstrategies. It is mediated through small interfering RNAs (siRNAs)which sequence-specifically trigger the cleavage and subsequentdegradation of their target mRNA. One critical factor is theability to deliver intact siRNAs into target cells/organs in vivo.This review highlights the mechanism of RNAi and the guidelinesfor the design of optimal siRNAs. It gives an overview of studiesbased on the systemic or local application of naked siRNAs or theuse of various nonviral siRNA delivery systems. One promisingavenue is the the complexation of siRNAs with the polyethylenimine(PEI), which efficiently stabilizes siRNAs and, upon systemicadministration, leads to the delivery of the intact siRNAs intodifferent organs. The antitumorigenic effects ofPEI/siRNA-mediated in vivo gene-targeting of tumor-relevantproteins like in mouse tumorxenograft models are described.

[学科分类] 基础医学