A RNA nanotechnology platform for a simultaneous two-in-one siRNA delivery and its application in synergistic RNAi therapy

Incorporating multiple copies of two RNAi molecules into a single nanostructure in a precisely controlled manner can provide an efficient delivery tool to regulate multiple gene pathways in the relation of mutual dependence.... [ view full abstract ]

Incorporating multiple copies of two RNAi molecules into a single nanostructure in a precisely controlled manner can provide an efficient delivery tool to regulate multiple gene pathways in the relation of mutual dependence. Here, we show a RNA nanotechnology platform for a two-in-one RNAi delivery system to contain polymeric two RNAi molecules within the same RNA nanoparticles, without the aid of polyelectrolyte condensation reagents. This strategy densely packs and co-delivers polymeric RNAi molecules, leading to the simultaneous silencing of two targeted mRNAs, of which biological functions are highly interdependent. In addition to assembly of polymeric, two types of RNAi molecules within single RNA nanoparticle, combination therapy for multi-drug resistance cancer cells, studied as a specific application of our two-in-one RNAi delivery system, demonstrates efficient synergistic effects for cancer therapy. This RNA nanoparticles approach has an efficient tool for a simultaneous co-delivery of RNAi molecules in the RNAi-based biomedical applications, and our current studies for its RNAi-based therapy present an efficient strategy to overcome multi-drug resistance caused by malfunction of genes in chemotherapy.