Lipid nanoparticles (LNPs) have become indispensable delivery vehicles for mRNA vaccines, gene therapies, and emerging genome-editing technologies. Despite their clinical success, the relationships between lipid molecular structure, nanoparticle organization, and biological activity remain incompletely understood. This knowledge gap continues to limit the rational design of next-generation LNP systems with improved potency, targeting, and intracellular delivery.
We are pleased to invite Marshall Scott Padilla, PhD, NIH K99 Postdoctoral Fellow in the Department of Bioengineering at the University of Pennsylvania and incoming Assistant Professor at Stanford University, to discuss how integrated chemical and biophysical approaches can reveal the structural principles that govern RNA lipid nanoparticle activity. In this webinar, Dr. Padilla will present a convergent strategy that connects modular lipid synthesis with high-resolution characterization of LNP supramolecular structure. He will first introduce a synthetic platform for developing Branched ENdosomal Disruptor (BEND) lipids, demonstrating how targeted branching modifications at lipid termini can substantially enhance endosomal escape, a major bottleneck in intracellular RNA delivery.
He will then explore how advanced biophysical techniques can uncover structural heterogeneity within LNP formulations. By combining analytical ultracentrifugation, multiangle light scattering, and small-angle X-ray scattering, his work reveals how particle morphology, internal organization, and formulation heterogeneity can correlate with RNA delivery performance across different biological applications.
Key points to be discussed during the session:
Dr. Jamie Spangler is an Associate Professor of Biomedical Engineering and Chemical & Biomolecular Engineering at Johns Hopkins University. Dr. Spangler earned a Bachelor of Science degree in Biomedical Engineering at Johns Hopkins University and went on to earn a PhD in Biological Engineering at MIT. After completing a postdoctoral fellowship at Stanford University School of Medicine, Dr. Spangler launched her independent research group at Johns Hopkins University in 2017, jointly between the departments of Biomedical Engineering and Chemical & Biomolecular Engineering. Her lab, located in the Translational Therapeutics and Regenerative Engineering Center at the School of Medicine, applies structural and mechanistic insights to re-engineer existing proteins and design new proteins that therapeutically modulate the immune response. In particular, her group is interested in engineering immune molecules such as cytokines, growth factors, and antibodies for targeted treatment of diseases such as cancer and autoimmune disorders.