ADVANCES IN mRNA VACCINE DEVELOPMENT: THE CENTRAL ROLE OF NANOTECHNOLOGY

Messenger RNA (mRNA) technologies have emerged as highly versatile platforms for vaccine development, enabling rapid antigen design, cell-free manufacturing, and adaptation to different biological targets. However, the successful translation of mRNA into effective vaccines strongly depends on the development of suitable delivery systems. Due to its intrinsic instability, susceptibility to enzymatic degradation, and limited ability to cross cellular membranes, naked mRNA requires efficient carriers to reach the cytoplasm and promote protein expression. Nanotechnology therefore plays a central role in mRNA-based applications. Lipid nanoparticles (LNPs) have become the leading delivery system, protecting RNA molecules while facilitating cellular uptake and endosomal escape. Their performance is highly dependent on formulation composition and physicochemical properties, including particle size, polydispersity, surface characteristics, encapsulation efficiency, lipid composition, and RNA-to-lipid ratio. Understanding the relationship between these parameters and biological performance is essential for improving potency, stability, safety, and tissue-specific delivery. At Bio-Manguinhos/Fiocruz, the establishment of an mRNA platform has integrated RNA design and production with analytical characterization, nanoparticle formulation, preclinical evaluation, and the development of manufacturing capabilities. This effort represents an important step toward strengthening national technological autonomy and health sovereignty by expanding local capacity to develop and produce advanced RNA-based technologies. Such capacity is particularly relevant for reducing dependence on external technologies, increasing preparedness for emerging and re-emerging health threats, and supporting more sustainable access to innovative health products. Beyond infectious disease vaccines, advances in RNA engineering and nanocarrier design are also expanding the potential of the platform toward therapeutic vaccines, protein expression, monoclonal antibodies, and other RNA-based medicines. The continued convergence of RNA biotechnology, biophysics, and nanotechnology will be fundamental for the development of the next generation of more stable, efficient, and accessible RNA-based products.