MRNA and pDNA delivery technologies for advanced therapeutic applications

The NanoMedicine Innovation Center (Director of the Center: Prof. Kazunori Kataoka) announced that Professor Satoshi Uchida (Principal Research Scientist), who is also an Associate Professor at Kyoto Prefectural University of Medicine, published a critical article on mRNA) and delivery of plasmid DNA (pDNA) by addressing various mRNA and pDNA delivery technologies, from basic research to therapeutic and clinical application. Pharmaceutics 2022, 14 (4), 810.

The enormous potential of non-viral mRNA and pDNA delivery systems has been demonstrated in the 2019 coronavirus (COVID-19) vaccines. Indeed, two mRNA vaccine formulations from Pfizer – BioNTech and Moderna were approved for emergency use within a year of the pandemic and have been administered to billions of people worldwide. In addition, a pDNA vaccine developed by Zydus Cadila has also received emergency approval in India, showing high efficacy in preventing infection in a large clinical trial. These successful examples encourage further research and development of mRNA and pDNA-based vaccines and therapies. Target areas are not limited to preventive vaccination for infectious diseases, but extend to therapeutic vaccines, genome processing, and protein replacement therapy.

However, current non-viral systems need improvement. For example, the relatively strong side effects of mRNA vaccines, including myocarditis, cause vaccine hesitation and discussions about repeated amplification. Thus, safer formulations are required for mRNA vaccines to become platforms for various infectious diseases. Meanwhile, therapeutic vaccines against cancer require more effective formulations to overcome the immunosuppressive nature of cancers. For other applications, including genome processing and protein replacement therapy, the delivery vectors will have to reach specific tissues and insert pDNA and mRNA without damaging the tissues. This Special Issue addresses the intense efforts to develop mRNA and pDNA delivery systems and their application in the treatment of diseases to meet these requirements.

The development of anti-virus delivery systems has two directions. One focuses on the general improvement of delivery processes, which includes the prevention of extracellular mRNA and pDNA degradation by nucleases, the intracellular targeting of mRNA and pDNA to desired sites, and the prolongation of protein expression by mRNA and mRNA pDNA. In the other direction, the delivery systems are precisely regulated for specific purposes, such as the approach of specific tissues and cells to achieve therapeutic goals and the stimulation of the innate immune system when used in vaccinations.

This paper provides comprehensive reviews of non-viral mRNA and pDNA delivery, examining the various mRNA and pDNA delivery technologies, from basic research to therapeutic and clinical application.


Nanomedicine Innovation Center

Magazine report:

Uchida, S., (2022) Plasmid DNA Delivery Systems and Messenger RNA for Advanced Therapies. Pharmaceutical.