For the last several years, we have been working on the structure of the so-called ionizable lipids used in lipid nanoparticles for RNA delivery. These molecules are cationic at low pH but neutral at higher pHs, which allows them to transition from water-filled vesicles under acidic conditions to lipid nanoparticles under physiological conditions. These properties are crucial to their ability to take up and deliver RNA as part of RNA therapeutics. Much of our work in this area have been performed in collaboration with Moderna Therapeutics.

Publications in this area:

  • Dehghani-Ghahnaviyeh S, Smith M, Xia Y, Dousis A, Grossfield A, Sur S., Ionizable Amino Lipids Distribution and Effects on DSPC/Cholesterol Membranes: Implications for Lipid Nanoparticle Structure, J Phys Chem B. 2023 Aug 10;127(31):6928-6939. doi: 10.1021/acs.jpcb.3c01296, pdf

  • Sreyoshi Sur, Alan Grossfield Theoretical estimate of the effective pKa of titratable lipids using continuum electrostatics bioRxiv 2026.04.06.716676; doi: https://doi.org/10.64898/2026.04.06.716676