Buffer Optimization of RNA-Lipid Nanoparticles: Stability, Structure & Function Across Solution & Frozen States
- A novel mechanism for lipid tail oxidation is shown to produce degradants that react with neighbouring cargoes to form RNA-lipid adducts
- Mildly acidic, histidine-containing buffers are shown to shut down this degradation pathway and improve siRNA-LNP stability for months at room temperature
- An understanding of how buffer attributes (identity, molarity, and pH) impact mRNA-LNP structure, morphology, and transfection efficiency enables rational design of frozen storage buffers