Seminar by Dr. Giovanni Settanni

Ruhr University Bochum, Faculty of Physics and Astronomy

Multi-scale simulations of RNA carriers in RNA therapeutics

mRNA-based therapies, which include, for example, vaccines and tumorimmunotherapies, are proving to be an extremely powerful and flexibletool against a relatively wide spectrum of diseases. mRNA, however, isan extremely labile poly-anion and complex delivery mechanisms arerequired to screen it from degradation and let it reach the cytoplasm ofthe target cells, where it will exert its function. Among the mostsuccessful delivery materials we can find lipid-based nanopartcles(LNP), made of a lipid formulation including ionizable cationic lipids,and ionizable cationic polymers, which, mixed with RNA, form polyplexes.However, even with the most effective delivery systems, the amount ofmRNA that is actually transfected to the target tissue remains low. Tohelp increase transfection efficiency of LNPs, as well as otheralternative materials, the structural and dynamical properties of thesedelivery systems have to be investigated, as well as their mechanism ofaction. Here, I'll show how  a combination of multi-scale moleculardynamics simulations have been used to help shed light on the way mRNAinteracts with cationic lipids in LNPs as a function of environmentalconditions, as well as, on how the LNP can fuse with the endosomalmembrane and deliver the mRNA cargo. I'll also show  how coarse grainedsimulations can be used to address the formation dynamics of polyplexes.