B3 - Immune sensing of conformational dynamics of mRNA structure and chemical editing

In the project “Immune sensing of conformational dynamics of mRNA structure and chemical editing”, we build on our combined expertise in nucleic acid chemistry and innate immune sensing of nucleic acids. Specifically, we aim to analyse how different chemical modifications of RNA can be applied to control dynamic conformational changes of mRNA secondary structures, and how this impacts the binding of the RIG-I-like receptors (RLRs) RIG-I and MDA5, the two major innate immune receptors involved in the recognition of viral RNA in the cytoplasm of virus-infected cells. With the help of the unique technological portfolio for structural analysis in this consortium, we will analyse how the dynamic molecular interaction of RLRs and RNA affects the formation of complex and dynamic signalosomes. We will apply this new insight to design high-quality mRNA therapeutics with predictable and robust immunological properties.