A new generation of large molecule drugs and nanoformulations (LMDs) is seeing an increased interest from the pharmaceutical industry. LMDs hold great promises for future development of therapeutics to treat diseases for which there are presently no cure. Among the most promising new generation of LMDs are nucleic acid therapeutics, administered either as free molecules or encapsulated in nano carriers. Despite recent technological advances, most LMD candidates suffer from poor bioavailability caused by a highly efficient hepatic blood clearance activity. A major objective of the project is to provide PoC for a novel concept allowing LMDs to evade unintended hepatic removal, affording more efficient delivery of these drugs to their intended target tissues.