SKM 2023 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 27: Computational Biophysics II
BP 27.2: Vortrag
Donnerstag, 30. März 2023, 15:15–15:30, BAR 0106
Lipid-based nanomaterials for RNA delivery investigated using molecular dynamics simulations — •David Noel Zimmer1 and Giovanni Settanni1,2 — 1Physics Department University of Mainz — 2Faculty of Physics and Astronomy Ruhr University Bochum
Lipid-based nanoparticles (LNP) are one of the most effective carriers in mRNA therapeutics. They are made of a mixture of ionizable, helper, and pegylated lipids encapsulating mRNA. While peg tends to remain on the surface of the nanoparticle, the structure of the core has not yet been well characterized. Experimental data point to a relative lack of order. The lipid composition of the formulation plays a key role in determining the effectiveness of the nano carrier. Small changes in the chemical structure of ionizable and helper lipids dramatically affect the efficiency of mRNA transfection. LNPs based on DLinDMA and DLinDAP, two ionizable lipids, showed significantly different transfection efficiencies, notwithstanding the very small difference in structure. Here, using a multiscale modeling approach, the behavior of lipid formulations based on these two lipids, cholesterol and DSPC or DOPE is examined aiming to provide an understanding of the interactions of lipids and mRNA. The simulations show that, despite DLinDAP binding affinity for mRNA is larger than DLinDMA, the overall interaction of the whole lipid formulation containing DLinDAP with mRNA is weaker, resulting in a larger average distance of the mRNA from the lipid bilayer. This shows that chemical optimization based only on mRNA-ionizable lipid interactions may not be sufficient for the development of more effective lipid formulations for RNA delivery.