Degradable glycopolymers for saRNA transfection

Gene delivery is a powerful technique that is often exploited in the treatment of several diseases. Currently, most gene vectors are expensive virus-based systems, which can trigger immune responses. As a cheaper and safer alternative to these systems, biodegradable polymers have been widely used to develop gene delivery systems due to their different desirable characteristics. In particular, poly(amido amine)s possess critical desirable characteristics, such as high cell transfection activity, that make them suitable and efficient for gene delivery. In this study, reducible poly(amido amine)s with different side chain lengths and glycopolymers have been developed to create polyplexes with self-amplifying RNA (saRNA). The cell transfection assay showed that sugar decorated poly(amido amine)s revealed better saRNA transfection activity than other non-decorated poly(amido amine)s. Nevertheless, no differences were obtained between the poly(amido amine)s with different side chain lengths. Overall, biodegradable poly(amido amine)s with different alcohols and sugars have been synthesized with high molecular weights and low molecular weight distributions to develop an optimal saRNA delivery system.