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Next-generation mRNA vaccine delivery system uses biodegradable polymers

A research team from POSTECH has developed a biodegradable polymer-based delivery system that efficiently transports mRNA. The study was recently in Biomaterials.

Since the COVID-19 pandemic, global interest in mRNA vaccines has surged. Among existing delivery methods, lipid nanoparticles (LNPs) are widely used due to their high efficiency. However, LNPs have a critical drawback: once injected, they can accumulate in the liver, potentially causing toxicity or triggering an excessive immune response, which in severe cases may lead to anaphylaxis.

To address this issue, the POSTECH research team explored the biodegradable polymer Poly β-amino ester (PBAE) as an alternative. PBAE has already been utilized for delivering siRNA, DNA, and mRNA and is safely degraded in the body. In this study, the team synthesized 55 types of PBAE polymers and used them to design novel polymer nanoparticles (PNPs) for mRNA delivery.

Experimental results demonstrated that the newly developed polymer exhibited higher mRNA delivery efficiency compared to conventional LNPs. Additionally, mRNA expression lasted up to four weeks—significantly longer than the typical five-day expression period of LNPs. Notably, the polymer ensured mRNA expression only at the injection site, with no detectable expression in the liver, thereby eliminating toxicity concerns.

Furthermore, in immune response experiments, the polymer effectively induced T-cell activity and demonstrated comparable performance to LNPs in generating neutralizing antibodies against the COVID-19 virus. These findings highlight the potential of polymer-based delivery systems as a safer and more efficient alternative for next-generation mRNA vaccines and gene therapies.

Professor Won Jong Kim stated, "Existing LNP-based delivery systems have a short expression period, limiting their use for therapeutic applications. However, the polymeric delivery system developed by our team extends mRNA expression up to a month, making it well-suited for therapeutic mRNA delivery.

"This research is significant as it introduces a novel polymeric material that could serve as an alternative to LNPs, whose patents are largely controlled by overseas entities."

The team was led by Professor Won Jong Kim from the Department of Chemistry at POSTECH in collaboration with the Korea Disease Control and Prevention Agency (KDCA).