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Home»News»Decoding the structure of nano ‘gene ferries’ to advance RNA drugs
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Decoding the structure of nano ‘gene ferries’ to advance RNA drugs

December 6, 2024No Comments3 Mins Read
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Decoding the structure of nano ‘gene ferries’ to advance RNA drugs
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PBAE mapping and model validation. (A) Molecular structure and pKa values at 25 °C of the PBAE copolymer with spermine (left) and oleylamine (right) subunit. Mapping to CG resolution within Martini 3 indicated by spheres. (B) Simulation snapshots of 9 kDa polymers in 10 mM HEPES at pH 5.4, simulated for 2.5 μs. Lipophilic components in gray, charged beads in red. Exemplary coloring corresponds to one polymer molecule per color. (C) Micelles formed of PBAE 70% OA as visible in TEM imaging. (D) Comparison of hydrodynamic diameters in DLS and simulation (MD) under low and high ionic strength buffer conditions. DLS results (n = 3) with mean ± SD of main peak below 20 nm by intensity. MD results are the mean of Dh averaged over the whole box, calculated from mean square deviation (msd) between 1.75 and 2.25 μs of simulated time. Credit: Nano Letters (2024). DOI: 10.1021/acs.nanolett.4c04291

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,” explains 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.”

See also  The Photovoltaic Properties of Gold Nanoclusters

Provided by
Ludwig Maximilian University of Munich



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