Virus-mimicking cell membrane-coated nanoparticles for cytosolic delivery of mRNA

Summary

This study tackles endosomal entrapment, a central barrier for mRNA and other cargos that must reach the cytosol after nanoparticle uptake. The design borrows the pH-triggered fusion mechanism of influenza A virus. Cells were genetically engineered to express viral hemagglutinin on their surface, and membranes from those cells were used to cloak mRNA-loaded nanoparticles. The resulting virus-mimicking particles carried the fusion protein as part of a biological coating intended to merge with the endosomal membrane under acidic conditions. In vitro, the formulation delivered mRNA into the cytosolic compartment and enabled expression of the encoded protein, demonstrating functional escape rather than uptake alone. In vivo administration also produced substantially higher protein expression in both local and systemic delivery settings. The principal finding is that a viral membrane-fusion function can be transplanted onto a cell-membrane-coated carrier to control the intracellular destination of its payload. This is significant because it offers a genetically programmable route to overcome a common nanodelivery bottleneck without changing the mRNA itself. The abstract does not specify the expression duration, safety of hemagglutinin display, target tissues, or performance against established delivery platforms.