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Molecular Insights into Cationic Polymer-Based RNA Delivery Systems

Researchers from Ludwig Maximilian University of Munich presented a study in Nano Letters on the molecular organization of cationic polymers used to deliver RNA drugs.

Olivia Merkel researches novel nano transport systems for the targeted local administration of drugs. Image Credit: Florian Generotzky / LMU

Cationic polymers show promise for delivering RNA therapeutics and vaccinations. They carry mRNA drugs in the same way as lipid nanocarriers do. The nanoscopic packing materials can successfully safeguard their contents while delivering them to the target cells.

We manufacture so-called ‘gene ferries,’ into which all kinds of therapeutic nucleic acids can be encapsulated for secure transport to the site of action.

Olivia Merkel, Chair Holder, Deputy Director, Department of Pharmacy, Ludwig Maximilian University of Munich

To increase the effectiveness of these gene ferries, it is necessary to understand how these particles form at the molecular level, encapsulate RNA, and then release it again - a feature that has yet to be extensively investigated.

Merkel is the principal investigator of a new study that has revealed new information on the structure of nanocarriers. The study was performed as part of her ERC research project RatInhalRNA (Rational and Simulation-Supported Design of Inhalable RNA Nanocarriers).

We manufacture so-called ‘gene ferries,’ into which all kinds of therapeutic nucleic acids can be encapsulated for secure transport to the site of action. Our research used a technique called coarse-grained molecular dynamics (CG-MD) to simulate and visualize the particles,” Merkel added.

The specific focus was on how polymer structure and environmental factors affect particle production. Wet lab studies with nuclear magnetic resonance (NMR) supported the simulations, confirming that CG-MD could offer deep insights into the structure and behavior of RNA nanoparticles.

Merkel concluded, “This study highlights CG-MD’s value in predicting and explaining the properties of RNA nano-formulations, which can help in designing better systems for future medical applications.

Journal Reference:

Steinegger, K. M. et. al. (2024) Molecular Dynamics Simulations Elucidate the Molecular Organization of Poly (beta-amino ester) Based Polyplexes for siRNA Delivery. Nano Letters. doi.org/10.1021/acs.nanolett.4c04291

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