New insights into cationic polymer structure in RNA drug delivery

LMU researchers have investigated how cationic polymers organize on a molecular level when transporting RNA drugs.

Cationic polymers are promising tools for transporting RNA therapeutics or RNA vaccines. Like lipid nanocarriers, they are used to deliver mRNA medicines. The nanoscopic packaging materials are able to effectively protect their load and deliver 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.”

Professor Olivia Merkel, Chair of Drug Delivery at LMU’s Faculty of Chemistry and Pharmacy

To further improve the effectiveness of these gene ferries, however, it is important to understand how these particles organize on a molecular level, encapsulate RNA, and release it again – an aspect which so far has not been fully examined. Merkel is principal investigator of a new study that has yielded fresh insights into the organization of the nanocarriers. The study was carried out as part of her ERC research project RatInhalRNA (Rational and Simulation-Supported Design of Inhalable RNA Nanocarriers) and the findings were recently published in the journal Nano Letters.

“Our research used a technique called coarse-grained molecular dynamics (CG-MD) to simulate and visualize the particles,” explains Merkel. The specific focus was on how changes in polymer structure and environmental conditions impact particle formation. Simulations were supported by wet lab experiments using nuclear magnetic resonance (NMR), which confirmed that CG-MD can reveal detailed insights into the structure and behavior of RNA nanoparticles. “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,” says Merkel.