Short interfering RNA (siRNA)-Based Therapeutics for Cartilage Diseases

Articular cartilage injury, as a hallmark of arthritic diseases, is difficult to repair and causes joint pain, stiffness, and loss of mobility. Over the years, the most significant problems for the drug-based treatment of arthritis have been related to drug administration and delivery. In recent years, much research has been devoted to developing new strategies for repairing or regenerating the damaged osteoarticular tissue. The RNA interference (RNAi) has been suggested to have the potential for implementation in targeted therapy in which the faulty gene can be edited by delivering its complementary Short Interfering RNA (siRNA) at the post-transcriptional stage. The successful editing of a specific gene by the delivered siRNA might slow or halt osteoarthritic diseases without side effects caused by chemical inhibitors. However, cartilage siRNA delivery remains a challenging objective because cartilage is an avascular and very dense tissue with very low permeability. Furthermore, RNA is prone to degradation by serum nucleases (such as RNase H and RNase A) due to an extra hydroxyl group in its phosphodiester backbone. Therefore, successful delivery is the first and most crucial requirement for efficient RNAi therapy. Nanomaterials have emerged as highly advantage tools for these studies, as they can be engineered to protect siRNA from degrading, address barriers in siRNA delivery to joints, and target specific cells. This review will discuss recent breakthroughs of different siRNA delivery technologies for cartilage diseases.