Posts classified under: Cores

RNA is a very special kind of drug. It offers potent, specific, and precise effects in lots of diseases. To realize its therapeutic talent, RNA must act inside chosen cells. Since RNA itself cannot travel in the body, we load it into nanoparticles or other carriers, which improve RNA delivery into cells of interest. To achieve such a precise addressing, we use “ligands”, i.e., molecules with affinity to specific binding sites or “epitopes” on surface of target cells.

Carrier geometry (size and shape), biomechanics (rigidity vs flexibility), mode of ligand attachment, all modulate targeting in a complex unpredictable way. Next, distinct ligands binding to the same epitope, may differently affect host defense or blood clearance. In some cases, ligand is not needed: carriers encounter countless blood components, some of which may serve as endogenous ligands. Further, carrier binding to some epitopes implicated in the internalization favors the ultimate addressing – interior compartments of the target cell.

Our mission is to support advancement of RNA biotheraptuics via enabling swift and low-failure solutions of targeting-related aspects – rationally designed and encompassed by chance by the Institute investigators. The Core’s resources – unique wealth of methodologies, equipment, reagents, and first of all, strong and friendly team of accomplished researchers immersed in collaborative projects on targeted drug delivery for several decades, will provide comprehensive support in identification of epitopes and ligands, molecular design and testing of the targeting RNA to diverse multitudes of desirable addresses in the body.

Delivery technologies such as lipid nanoparticles (LNP) offer significant advantages over the delivery of free RNA for various RNA therapeutic, vaccine, and basic science applications. LNP technologies protect and prevent RNA degradation in the bloodstream, avoid renal clearance of RNA, enable cellular targeting through ligand functionalization and/or the tailoring of LNP physicochemical properties, and mediate cellular entry and endosomal escape to enable RNA release in the cytoplasm.

The mission of the Lipid Nanoparticle (LNP) Core of the Institute for RNA Innovation is to design and implement novel LNP technologies for a range of RNA therapeutic, vaccine, and basic science applications for research groups across the University of Pennsylvania and the Children’s Hospital of Pennsylvania. The LNP Core offers a wealth of expertise and resources including combinatorial chemistry of ionizable lipids and polymers, microfluidic technologies for LNP formulation, as well as LNP characterization and scaleup for RNA vaccine and therapeutic studies.