ZBP-Kolloquium

Prof. Dr. Joachim O. Rädler (LMU München)
Title: pH-Dependent Mesophases Determine Lipid Nanoparticle Function: Toward Controlled Gene Expression and Cellular Reprogramming
Time: 14:15 (refreshments at 14:00)
Location: Campus SB, Building C6 4, room 0.09 (Hörsaal II)
Host: Dr. Philipp Hövel

Abstract: Lipid nanoparticles (LNPs) are the leading platform for nucleic acid delivery. We show that pH-driven structural transitions of cationic ionizable lipids (CILs)—from inverse cubic (Fd3m) to inverse hexagonal (HII) phases—exist in model systems and appear to be correlated with gene delivery efficiency. Using high-resolution small-angle X-ray scattering, live-cell imaging on single-cell arrays (LISCA) and mathematical modeling we establish self-regulated and noise-buffered gene expression. We apply LNP delivery to transiently reprogram migratory phenotypes as a powerful tool for synthetic biology.

Müller, J.A., N. Schäffler, T. Kellerer, G. Schwake, T.S. Ligon, and J.O. Rädler. 2024. Kinetics of RNA-LNP delivery and protein expression. European Journal of Pharmaceutics and Biopharmaceutics. 197:114222.
J. Philipp, A. ... L. Lindfors and J.O. Rädler. 2023. pH-dependent structural transitions in cationic ionizable lipid mesophases are critical for lipid nanoparticle function,PNAS Vol. 120 No. 50 e2310491120.