Regensburg 2025 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 19: Membranes and Vesicles II

BP 19.6: Vortrag

Mittwoch, 19. März 2025, 10:45–11:00, H46

Investigating Endosomal Escape Mechanisms of PEI-DNA Polyplexes with Computer Simulations — •Jonas Lehnen¹, Friederike Schmid¹, and Giovanni Settanni² — ¹Physik, Johannes Gutenberg Universität, Mainz — ²Physik, Ruhr-Universität Bochum

Nucleic-acid-based therapeutics have recently demonstrated their potential thanks to the successful COVID-19 vaccination campaign. They have been already approved or in the latest stages of clinical trials as remedies for a broad range of pathologies, including cancer and genetic diseases. These approaches make use of complex delivery vehicles to take the nucleic acids to the target tissues. The presently used lipid-based nanoparticles still face a relatively low delivery rate and side effects. Polyplexes, formed by the aggregation of cationic polymers with the anionic nucleic acids, may provide a valid alternative. The transfection mechanism for these polyplexes is an ongoing topic of research. We use coarse grained molecular dynamics simulations to investigate contributing factors to the endosomal escape process which is a crucial limiting step in the transfection process. Our simulations model an endosome containing a polyplex, evaluating key factors such as the surface tension of the endosome caused by osmotic swelling and the interactions between the polyplex and the endosomal membrane, which are key factors in the predominant theories.

Keywords: endosomal; escape; vesicle; polyplex; simulation