Multifunctional polymeric nanoparticles for RNA delivery: from carrier design to cancer immunotherapy

Abstract

The lack of safe and efficient gene delivery system limits the efforts to develop new RNA drugs to combat various diseases including genetic disorders, viral infections and cancer. Even though substantial success has been made with polymeric vectors, their applications has been restricted by the inefficient in vivo delivery of RNA therapeutics. With the recent technological advances and better understanding of the fundamental biological mechanisms for different diseases, development of multifunctional polymeric delivery platforms that will efficiently transport RNA therapeutics to the target site, are becoming the critical step for clinical translation. In this thesis, we have investigated different newly synthesized polymers for siRNA and mRNA delivery. With employing copper-free click chemistry, we were able to design and build multifunctional polymeric delivery system to fulfill different applications. The delivery target was from tumor cells with siRNA gene silencing to antigen presenting cells (DCs) for mRNA cancer vaccines.