(555a) Optimization of Liposome-Hollow Gold Nanoparticle for mRNA Delivery

Veeren, A., University of Minnesota
Osborn, M., University of Minnesota
Merkel, S., University of Minnesota
Shin, J., University of Minnesota
Zasadzinski, J. A., University of Minnesota
mRNA therapy has gathered great interest because of its potential role for the transient modification of immune cells for treatment of an array of diseases. However, the main obstacle preventing routine mRNA immune cell transfection is the lack of a high viability, high efficiency, high throughput delivery system. Due to its sensitivity towards catalytic hydrolysis, unprotected mRNA cannot be delivered by itself. We propose encapsulating mRNA in neutral liposomes decorated with cell internalizing peptides and hollow gold nanoshells (HGN). We use passive entrapment of lightly condensed mRNA in phospholipid-cholesterol bilayer liposomes incorporating polyethylene-glycol-lipid tethered TAT and HGN. Following TAT induced endocytosis, we can irradiate the cells with picosecond pulsed near infra-red light to induce vapor nanobubbles around the HGN that can rupture both the liposomes and the endosomes, thereby releasing the MRNA to the cell cytoplasm, where the mRNA can produce the proteins of interest. We will present our work toward the realization of this light triggered mRNA delivery system.