RNA-based therapies have shown promise in a wide range of applications, from cancer therapy, treatment of inherited diseases to vaccination. Encapsulation of RNA into ionizable lipid (IL) containing lipid nanoparticles (LNPs) has enabled its safe and targeted delivery. We present here the simulations of the self-assembly process of pH-sensitive RNA-carrying LNPs and their internal morphology. At low pH, the simulations confirm a lipid core encapsulating RNA in the hexagonal phase. Our all-atom and coarse-grained simulations show that an RNA molecule inside an LNP is protected from interactions with ions by being enveloped in the charged ILs. At neutral pH, representing the environment after LNP administration into human tissues, LNPs expelled most of the encapsulated RNA and water and formed separate bulk IL-rich and ordered the helper-lipid-rich phase. Helper lipids arranged themselves to be in contact with RNA or water. The presented models provide atomistic understanding of the LNP structure and open a way to investigate them in silico, varying the LNP composition or interacting with other biostructures aiming at increasing the efficiency of RNA-based medicine.

IT4Innovations VŠB Technical University of Ostrava 17 listopadu 2172 15 Ostrava Poruba 708 00 Czech Republic

Regional Centre of Advanced Technologies and Materials Czech Advanced Technology and Research Institute Palacký University Olomouc Šlechtitelů 27 Olomouc 779 00 Czech Republic

Citace poskytuje Crossref.org

Computational Methods for Modeling Lipid-Mediated Active Pharmaceutical Ingredient Delivery