Speaker
Description
Lipid nanoparticles (LNPs) have enabled the rapid development of RNA-based medicine in vaccination, cancer treatment and the therapy of rare diseases. These systems encapsulate RNA within assemblies of ionizable lipids (ILs), helper lipids, and a PEG shell, achieving high loading efficiency through electrostatic interactions of ILs with RNA, while maintaining low cytotoxicity due to the neutral charge of ILs under physiological conditions. Despite intense efforts in ILs design aiming to improve the RNA delivery efficiency, progress is hindered by a limited molecular-level understanding of LNP structure, its pH induced changes, and the mechanisms underlying endosomal escape.
Multiscale molecular dynamics (MD) simulations provided an important and detailed insight into the LNP structure. However, the systems of interest contain a mixture of variously charged lipids and nucleic acids in LNP and possible interacting biocompartments, all dynamically diffusing, therefore changing their composition definition. Their dynamical analyses offer new challenges and opportunities in the possible extracted message of the behavior of LNPs.
Here we present the combined all atom and coarse grained simulations decoding the role of LNP composition of the adopted LNP phase, its curvature and mobility. We focus on role of the structure of IL, the ratio of individual lipid components in LNP and of RNA under different environmental conditions. The dynamic decoding of the LNP internal structure offers a detailed insight into the role of its individual components on the resulting particle.