One-component ionizable amphiphilic Janus dendrimers as a delivery platform for efficient mRNA vaccine development.

There have been rapid advances in nucleoside-modified messenger RNA-based vaccines, particularly during the SARS-CoV-2 pandemic, demonstrating a rapid and cost-effective approach for addressing infectious diseases. A major challenge remains in developing a delivery system that protects mRNA from degradation and facilitates its passage through tissue and cellular barriers. Current four-component lipid nanoparticles enable efficient endosomal escape and are a pivotal technology for the delivery of mRNA vaccines. However, challenges such as stability, availability, durability, and adverse effects persist. We have developed a self-assembling one-component ionizable amphiphilic Janus dendrimers (IAJD) delivery system with naturally occurring amino heads, capable of efficiently delivering mRNA to the spleen and lymph nodes. This single-component system simplifies synthesis, reduces development complexity, and enables rapid global distribution of mRNA vaccines during pandemics. As a proof of concept, one-component IAJD97, formulated with mRNA encoding norovirus mRNA capsid protein, demonstrates the potential of IAJDs as efficient delivery platform for mRNA vaccines, advancing their effectiveness and expanding applications to improve public health outcomes.