Gene therapy progress and prospects: synthetic polymer-based systems

Low efficiency, significant toxicity, polymer polydispersity and poorly understood delivery mechanisms have initially plagued the field of polymer-based gene therapy. Numerous strategies have helped to improve polyplexes, including the development of biodegradable polymers with reduced toxicity, incorporation of cell targeting, surface shielding and additional transport domains for effective and specific delivery, or improved chemistry for syntheses of polymers with uniform size and topology. Combined biooptical imaging and bioinformatics, providing insights into transfer bottlenecks, have helped to design improved polyplexes. Bioresponsive multifunctional polymers adapt in a dynamic manner to delivery barriers for efficient transfer of pDNA or siRNA to the target site.