Thermodynamically Stable Nanotubular mRNA Carriers made of Self-Adjusting Peptide Building Blocks

While mRNA delivery technology holds significant promise, storage and safety-related problems still exist, which arise from the inherently low thermodynamic stability of conventional mRNA carriers. The existing mRNA carriers have generally spherical structures. Considering the filamentous nature of mRNAs and the exceptional thermodynamic stability associated with nanotubes among nano-assemblies, we could dramatically enhance the thermodynamic stability by developing mRNA carriers in the form of nanotubes. Through cooperative interactions, mRNA and peptides were fabricated into rigid nanotubes that resemble tobacco mosaic virus. The fluttering and irregular mRNA strand was coated by a single layer of peptide building blocks. The crucial factor in developing the mRNA nanotube lies in designing self-adjusting supramolecular building blocks (SABs). SABs contain α-helical coiled coils, that incorporate two contrasting properties, namely dynamic flexibility and stiffness, within a single molecule. mRNA nanotubes with bound ligands for targeting exhibited high uptake efficiencies and the tunable transfection efficiencies in mammalian cells. Consequently, mRNA nanotubes will provide underlying technology in advancing the development of more stable and safe mRNA vaccines and therapeutics.