Recent Advances in Engineering Carriers for siRNA Delivery

RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical are hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, the recent advances in siRNA carriers consisting of lipids, polymers, and polymer-modified inorganic particles for cancer therapy are summarized. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. It is believed that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications. RNA interference (RNAi) gene therapy has been an important methodology to treat various incurable diseases. Successful siRNA delivery via carriers is a determining factor affecting the therapy result. Accordingly, recently progress on three major types of siRNA carriers have been reviewed. They include lipids, cationic polymers, and polymer-inorganic hybrids. Additionally, current challenges associated with RNAi gene therapy have been discussed.image