Unravelling LNP endosomal escape

LNP are versatile drug and gene delivery particles. Examples of successful LNP formulation are the Comirnaty and mRNA-1273 Covid19 vaccines. Even though these are successful, cellular internalisation remains to be the man limiting factor on their therapeutic efficiency forcing high concentration doses with unwanted side effects. In-depth investigations using endosomal membrane mimics are limited due to the constrains of these systems. To meet this need, we developed an assay that monitors single LNP binding events to a supported lipid bilayer (SLB) designed to mimic the endosomal membrane. The SLB is formed on top of a nanoporous substrate that creates edges and compartments that facilitate molecular incorporation beneath the SLB. Neutron reflection will be used to demonstrate that the cationic lipid in LNP fuse with the membrane and that the cargo is delivered beneath the membrane.