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BP: Fachverband Biologische Physik

BP 19: Membranes and Vesicles II

BP 19.3: Vortrag

Mittwoch, 19. März 2025, 10:00–10:15, H46

Engineering asymmetric lipid vesicles for protein delivery — •Kevin Jahnke, Chenjing Yang, and David Weitz — Harvard University, Cambridge, USA

The delivery of therapeutics to cells is crucial for the treatment and prevention of diseases. To enhance targeting and protect therapeutics from degradation, they are often encapsulated into drug delivery vehicles like lipid nanoparticles, liposomes and viral vectors. However, there is no universal vehicle for all cargo types including small molecules, nucleic acids and proteins. Here, we present a method for engineering lipid vesicles with asymmetric leaflets and demonstrate their ability to deliver mRNA and proteins to cells (Yang,.., Weitz, Jahnke; biorxiv 2024). We show that leaflet asymmetry modulates the biophysical properties of lipid vesicles, leading to an enhanced vesicle uptake by cells, and an up to 5-fold increased transfection efficiency with mRNA. Additionally, we show that asymmetric vesicles can deliver a variety of proteins, including the gene-editing protein Cas9 and Cas9/sgRNA complexes. By modifying lipid vesicles with polysaccharides (Jahnke et al.; PNAS 2024) or the engineering of lipid-polymer hybrid vesicles, we further achieve the targeted delivery to specific cell types. Our method and findings expand the parameter space for engineering drug delivery vehicles and demonstrate the pivotal role of leaflet asymmetry in determining the biophysical properties of lipid vesicles. Consequently, our work leads to many applications, including the formation of more efficient, universal drug carriers that enable the delivery of proteins to cells.

Keywords: Lipid vesicles; Membrane biophysics; Drug delivery; Targeting; Polymersomes