Switch out the PEG - optimization of polysarcosine lipid nanoparticles for mRNA delivery

Tuesday 08:00 PDT / 11:00 EDT / 16:00 BST / 17:00 CEST

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Switch out the PEG - optimization of polysarcosine lipid nanoparticles for mRNA delivery

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Lipid nanoparticles (LNPs) have emerged as the leading platform for mRNA delivery, yet their biological performance depends sensitively on the structural and compositional features of the formulation. A major challenge lies in the use of PEG-lipids, which, despite their stabilizing function, are associated with adverse immunological effects such as accelerated blood clearance and hypersensitivity. In this talk, we will discuss polysarcosine-based lipids as a promising alternative to PEG for the stabilization of mRNA-loaded LNPs. By combining design-of-experiments methodologies with predictive modeling, we used Sunscreen to systematically assess how variations in polymer architecture and lipid structure influence nanoparticle properties and delivery efficiency. This approach enabled the identification of quantitative structure–activity relationships and provided a framework for the rational optimization of LNP formulations. These findings illustrate the value of data-driven strategies in the development of improved nucleic acid delivery systems.

Fabian Link

PhD Student at LMU Munich

Fabian Link is a PhD student at the Institute of Pharmaceutical Technology at LMU Munich in the group of Prof. Olivia Merkel and a member of the CPC-M site. With a background in chemistry, his research focuses on the development of lipid nanoparticles (LNPs) for RNA delivery. His work combines machine learning, statistical modeling, and experimental design with wet-lab formulation and biological evaluation to reduce the experimental complexity of LNP development. By integrating data-driven approaches with hands-on experimentation, he aims to accelerate the rational design of RNA delivery systems for future nanomedicine applications.

Ross Walton

Senior Application Scientist for Analytics at Unchained Labs

Ross Walton is a Senior Application Scientist for Analytics at Unchained Labs. He has published works on single-particle protein analysis by transmission electron microscopy and the interaction of the innate immune system and viruses in cancer. He did his undergraduate work at UC Berkeley and earned his PhD in Molecular Genetics and Microbiology from Duke University.

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