(609f) RNAi therapy using Janus base nanotubes against cartilage degradation

Osteoarthritis (OA) is a common cause of cartilage degeneration and disability. Currently, there are no clinically approved therapeutics to prevent or treat OA. As a Nobel prize discovery, RNA interference (RNAi) offers great potential to silence a single gene to inhibit disease progression. However, translation into a clinical setting makes it difficult by the lack of efficient carrier systems for therapeutic siRNA, which major limitation of RNAi therapeutics is endosomal entrapment of the delivered siRNA. Lipid nanoparticles can efficiently deliver RNA cargos into various types of cells, but they present poor endosomal escape ability so that a majority of delivered siRNA is not functional. Cationic polymers can efficiently escape from endosomes, but they have covalently linked polymers and usually have low biodegradability and high cytotoxicity. Herein, we developed a novel delivery vehicle based on DNA-inspired Janus base nanotubes (JBNTs) with excellent endosomal escape and low cytotoxicity. Importantly, JBNTs can load siRNA in rod-shaped nanoparticles which can effectively penetrate articular cartilage and inhibit expression of inflammation genes. We have demonstrated the great potential of using JBNTs to achieve RNAi therapy to inhibit cartilage degradation via a pre-clinical OA model.