Small-Molecule End-Groups of Linear Polymer Determine Cell-type Gene-Delivery Efficacy

Gene delivery has the potential to treat a range of inherited and acquired diseases. Research has primarily focused on the use of viral vectors for this purpose, due to efficient infection of cells with viruses as well as long-term gene expression. However, the use of viral vectors for gene therapy is limited by safety concerns, production/manufacturing challenges, and limited nucleic acid carrying capacity [1, 2]. Thus, increased attention has been focused on biomaterials including cationic polymers as gene transfection agents [3-5] due totheir electrostatic interactions with plasmid DNA to form cationic nanoparticles. Polymers, including polyethylenimine (PEI), are useful in a variety of gene therapy applications [6-10]. One promising class of polymers, poly(β-amino ester)s (PBAEs), are degradable and have enhanced delivery compared to PEI [11-13]. Recent studies show that the amine-terminated polymers are generally more effective at promoting cellular uptake and DNA delivery than their acrylate-capped counterparts [14, 15].