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Since the discovery regarding interference phenomenon, 20 years ago, RNA interference became standard method to suppress a gene expression into in vitro tests. Nowadays, the point of interest lies in vivo studies. The RNAi could be used as strong tool in specific therapy going from viral infection to cancer, if only the RNAi would have a proper structure. The main obstacle to RNAi potential therapeutic action is due to a difficulty small interfering RNA (siRNA) at the level of its action in vivo. An effective delivery strategy of siRNA must consider some limitations: (i) poor stability, (ii) undesirable non-specific immune response, (iii) a distribution in non-targeted tissues. The development of such a strategy requires a careful understanding of all the mechanisms of action of RNAi, engineering developed to overcome barriers to the delivery of siRNA, the site of action, and finally a clinical trial. This analysis allows us to offer a perspective on the therapeutic use of siRNA in human.
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