Synthesis and characterization of novel polyamidoamine for gene delivery

Abstract

The importance and significance of gene therapy has significantly influence interests in development of novel therapeutic genes as well as promising delivery vectors. Synthetic gene delivery vectors have attracted enormous attention in recent decades because of their ease of manufacturing, targettability, and scaling up. However, certain issues like high cytotoxicity and inferior transfection efficiency, like polyethyleneimine (PEI) example, has limited their applications. Still, researchers are still heavily exploiting PEI for cell specific gene delivery. In this project, we developed two novel polyamidoamine containing various types of protonable amines with biodegradable disulfide bonds capable of mediating high gene delivery in mammalian cells namely polymer-1 and polymer-2 (P1 and P2). Both polymers were evaluated for their ability in binding, condensing, and delivering gene to cells. The better of the two, polymer-2, was taken forward to be conjugated with polyethylene glycol (PEG) and targeting ligands for gene delivery to specific cells. The resulting polymer conjugates were able to induce efficient gene delivery in HepG2 cells expressing asialoglycoprotein receptor and 4T1 cells overexpressing folate receptor. The polyamidoamine developed are promising gene delivery carriers for specific cells.