Advances in lipid-based platforms for RNAi therapeutics

Sequence-specific gene silencing, known as RNA interference (RNAi), is a natural process that can be exploited for knocking-down specific genes involved in the insurgence/development of pathological processes. In 2001 the discovery that small interfering RNA (siRNA) can induce gene silencing without immunoresponse turned RNAi into a promising technique for the control of post-transcriptional gene expression. Nowadays, the major challenge remains infusion in vivo. Therefore, vehicles providing protection and selective transport are to be developed for efficient systemic delivery. The most used vectors are lipid-based, offering a wide range of biocompatible formulations. Here their application in molecular medicine is discussed, especially with regard to recent clinical trials where conventional therapies have failed. The role played by extended physicochemical characterization for the success of RNAi therapeutics is also evidenced.