Cationic liposome formulations for RNAi-based validation of therapeutic targets in rheumatoid arthritis.

Abstract

Several molecules have been identified as critical mediators of chronic inflammation in immune system-mediated disorders such as rheumatoid arthritis (RA), and biological therapies targeting these molecules have been developed during the past two decades. Compared with conventional therapies, anti-TNF biotherapies have greatly improved the treatment of patients with RA, and several biological agents with distinct mechanisms of action are under development. Despite significant advances in this field, unmet medical needs remain. RA is the prototype disease for the evaluation of targeted therapies, and various novel genes have been described as being critically involved in disease pathogenesis. Thus, a novel area of research has recently emerged in the field of RA therapy, involving the genetic screening and validation of novel candidates in vivo using RNAi. Among the vehicles for the efficient targeting of macrophages, which play a critical role in disease chronicity, cationic liposomes represent the most promising option for the safe and specific use of RNAi in vivo. This review discusses the role of cationic liposomes as a mechanism for the systemic administration of siRNAs in the validation of RA therapeutic targets.