Affiliation: Inserm, U 844, INM, Hopital Saint Eloi, F-34295 Montpellier, France; Universite Montpellier1, UFR de Medecine, F-34000 Montpellier, France; CHU Lapeyronie, service Immuno-Rhumatologie, F-34000 Montpellier, France.
RNA interference (RNAi) is an endogenous process initiated by short double stranded RNAs, which results in sequence-specific posttranscriptional gene silencing. Since its discovery RNAi has become the most widely used experimental tool providing powerful and sequence-specific knockdown of protein expression to elucidate the function of genes. The possibility of blocking the expression of any protein carries huge expectations for potential therapeutic applications in a wide range of diseases. For clinical development, however, the use of RNAi-based therapeutics has to overcome major drawbacks and disadvantages, mainly targeted delivery and safety issues. This review summarizes the current status of progress made in the development of efficient in vivo silencing; focusing on both viral and non viral delivery strategies, and provides an overview of specifications for anti-inflammatory RNAi-based gene therapy in preclinical models of immune- mediated inflammatory disorders such as rheumatoid arthritis, skin disorders and inflammatory bowel diseases.