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Polymer library for RNA-based therapeutic approaches

12 Jul 2024

The research group of LMU pharmacist Olivia Merkel has optimized the synthesis of polymer nanoparticles to facilitate the targeted distribution of RNA agents in the body.

Portrait of Prof. Dr. Olivia Merkel

Olivia Merkel is the lead author of the newly published study. | © Florian Generotzky / LMU

RNA therapy with polymer nanoparticles is considered a promising approach for the treatment of various illnesses. It involves the use of polymers as “nanocarriers” to transport RNA drugs precisely to the correct target cells. Manufacturing such polymers, however, has proven to be complex and difficult.

In a recent study by the research group of Olivia Merkel, Professor of Drug Delivery in the Department of Pharmacy at LMU, so-called spermine-modified poly(beta-amino esters) (PBAEs), a polymer type that is frequently used for the formulation and delivery of nucleic acids were focused on. “We synthesized and characterized a library of 27 different polymers, taking into account various factors such as the ratios of starting materials, the temperature, and the reaction time,” explains Merkel.

Factors that significantly influence the polymerization of polybeta-amino ester block copolymers can be identified by statistically evaluating a library of 27 materials. A computer program can then be used to identify polymers that are particularly suitable for therapeutic RNA delivery.

Factors that significantly influence polymerization are identified by statistical analysis of a library of 27 polymers that are particularly suitable for therapeutic RNA delivery. | © Merkel Lab

A design-of-experiment approach, whereby the significant factors of experiments are identified by means of statistical analyses, enabled the researchers to derive a wealth of information out of just a few experiments. The polymers were chemically analyzed to understand their composition and molecular properties. In addition, a computer-based protocol was developed to better capture the complex process of polymerization and predict it for future syntheses. “Our research helps to improve the quality, efficiency, and precision of RNA drugs,” says Merkel regarding the results of the study.

Adrian Kromer, Felix Sieber-Schäfer, Johan Farfan Benito & Olivia M. Merkel: Design of Experiments Grants Mechanistic Insights into the Synthesis of Spermine-Containing PBAE Copolymers. ACS Publications 2024

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