[Responsive DNA origami for mRNA delivery]

mRNA technology has emerged as a crucial tool in fields including vaccinology, gene therapy, and regenerative medicine. However, mRNA is susceptible to rapid degradation by ribonucleases (RNases) in physiological environments, and its large molecular weight and negative charge hinder its transmembrane delivery into cells. Existing delivery systems face key bottlenecks such as insufficient serum stability, limited cellular uptake efficiency, and a lack of controlled intracellular release mechanisms. Consequently, there is an urgent need to develop novel delivery platforms that offer both robust protective capabilities and precisely controlled release. In this study, a barrel-shaped DNA nanostructure was constructed using DNA origami technology, and its structural integrity was verified using agarose gel electrophoresis, atomic force microscopy (AFM), and transmission electron microscopy (TEM). The stability of the mRNA-origami complex was further assessed under 10% fetal bovine serum (FBS) conditions, and its cellular uptake behavior was evaluated in HT29 cells. Building on this platform, a stimulus-responsive release strategy was further developed by incorporating an ultraviolet-activatable PC linker, enabling photo-controlled release and thereby achieving responsive mRNA translation expression. The constructed photo-controlled release system allows programmable intracellular dissociation and release upon specific stimuli. By combining carrier structure optimization with a stimulus-responsive mechanism, a comprehensive intelligent mRNA delivery strategy was established. This study provides novel design concepts and experimental paradigms for constructing nucleic acid delivery systems with high stability, efficient cellular uptake, and controllable release capability.