Structure determination of complex, therapeutically relevant lipid nanoparticles for RNA delivery

Lipid nanoparticles (LNPs) have evolved into smart multifunctional carriers for drug deliverymost notably in the thriving field of siRNA and mRNA therapeutics for treatment of diseases not curable today. Characterization of LNP bulk and in particular surface structure is of eminent importance to understand their interactions andtherapeutic function.The structure determination of complex lipid-based RNAnanoparticles is challenging due to their finite size, intrinsic disorder, hierarchical structureat different length scales, low lipid-RNA contrast and fast dynamics. We propose to use SANS and selective deuteration in combination with different solution isotopic contrasts is the only way to determine the location of the different compounds within this type of complex LPNs. New sophisticated modelling tools will be adapted and further developed to gain new insight in the structure.