High resolution solution biophysics for identifying lipid nanoparticle trends in vivo and ex vivo

Introduction: Lipid nanoparticles (LNPs) are potent delivery vehicles that have accelerated the translation of RNA therapeutics and led to the FDA-approval of mRNA COVID-19 vaccines. However, one major barrier is the low sensitivity of current characterization techniques. In this study, we combined standard characterization techniques with SV-AUC, FFF-MALS, and SEC-SAXS using a library of gold-standard LNP formulations prepared by microfluidic mixing or bulk mixing. We then performed in vivo and ex vivo transfection experiments and developed physico-biological trends using the combined results.