Multifunctional rolling circle transcription-based nanomaterials for advanced drug delivery

As the up-and-comer in the development of RNA nanotechnology, RNA nanomaterials based on functionalized rolling circle transcription (RCT) have become promising carriers for drug production and delivery. This is due to RCT technology can self-produce polyvalent tandem nucleic acid prodrugs for intervention in intracellular gene expression and protein production. RNA component strands participating in de novo assembly enable RCT-based nanomaterials to exhibit good mechanical properties, biostability, and biocompatibility as delivery carriers. The biostability makes it to suitable for thermodynamically/kinetically favorable assembly, enzyme resistance and efficient expression in vivo. Controllable RCT system combined with polymers enables customizable and adjustable size, shape, structure, and stoichiometry of RNA building materials, which provide groundwork for the delivery of advanced drugs. Here, we review the assembly strategies and the dynamic regulation of RCT-based nanomaterials, summarize its functional properties referring to the bottom-up design philosophy, and describe its advancements in tumor gene therapy, synergistic chemotherapy, and immunotherapy. Last, we elaborate on the unique and practical value of RCT-based nanomaterials, namely "self-production and self-sale", and their potential challenges in nanotechnology, material science and biomedicine.