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DY: Fachverband Dynamik und Statistische Physik
DY 37: Statistical Physics of Biological Systems II (joint session BP/DY)
DY 37.10: Talk
Thursday, March 21, 2024, 12:00–12:15, H 1028
Polyplex formation process investigated by coarse-grained molecular dynamics simulations — •Jonas Lehnen1, Friederike Schmid1, and Giovanni Settanni2 — 1Institute of Physics, JGU Mainz, Germany — 2Faculty of Physics and Astronomy, Ruhr University Bochum, Germany
Messenger RNA vaccines have proven invaluable in the fight against the COVID-19 pandemic. Among the vehicles for non-viral gene delivery Polyethylenimine (PEI) has attracted attention due to its high transfection efficiency. PEI binds to negatively charged mRNA forming polyplexes. The size and characteristics of these nanoparticles (NP) depend on the pH used for their assembly as well as salt, PEI and RNA concentration. Small NP have been shown to be critical for high transfection efficiency. We use coarse-grained molecular dynamics simulations with explicit ions to examine the effects of the various factors determining polyplex size and gain a better understanding of the processes involved in their formation. In agreement with available experimental data, our simulations show how small NP sizes are obtained when mixing RNA with an amount of PEI largely exceeding the requirement for RNA neutralization. Further, we present insight on the importance to focus not only on stoichiometric ratios of RNA and PEI but also on the overall concentration. Finally we present a kinetic and a thermodynamic mechanism which can explain the experimental results, and could be leveraged to reliably produce small NPs, minimizing the amount of necessary PEI, which, in large doses, can be toxic.
Keywords: PEI; RNA; coacervation; nanoparticle; simulation