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Curr Opin Mol Ther. 2007 Aug;9(4):345-52.

Nonviral in vivo delivery of therapeutic small interfering RNAs.

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  • 1Philipps-University Marburg School of Medicine, Department of Pharmacology and Toxicology, Karl-von-Frisch-Strasse 1, D-35033 Marburg, Germany.


Since its discovery in the late 1990s, RNA interference (RNAi) has gained much attention as a powerful strategy for silencing activity. Instrumental for this naturally occurring targeting mechanism is the intracellular presence of a target gene-specific small interfering RNA (siRNA). Therefore, the in vivo delivery of highly specific siRNA molecules represents one major goal in the further development of RNAi-based approaches for clinical applications. For the non-viral delivery of siRNAs, except for local or topical administration, various routes of application and delivery vehicles/strategies have been explored so far, including the systemic injection of pure, unmodified or chemically modified siRNAs, physical methods such as hydrodynamic injection or electropulsation, encapsulation of siRNAs in liposomes, lipoplexes or cationic lipids, formation of nanoplexes through complexation of siRNAs in cationic or other carriers, or chemical coupling of siRNAs to specific carrier molecules. Therefore, approaches to establish the clinical application of RNAi may rely on a combination of biosciences and nanotechnology; in particular, for the identification of optimal siRNAs against optimal target molecules, and the development of sophisticated delivery systems.

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