mRNA: A Novel Tool for Cell Reprogramming and Differentiation in Regenerative Medicine

The COVID-19 pandemic generated interest in the medicinal applications of messenger RNA (mRNA). It is expected that mRNA can be applied not only to vaccines but also to regenerative medicine. In the synthesis of mRNA, by-products that do not have a 5' cap structure are generated, and it is generally difficult to remove them. The by-products bind to the host's immune receptors and cause an inflammatory response. To solve this problem, the introduction of chemically modified nucleosides, such as N1-methyl pseudouridine and 5-methylcytidine, has been reported by Karikó and Weissman, opening a path for the practical application of mRNA for vaccines and regenerative medicine. Yamanaka reported the production of induced pluripotent stem cells (iPSCs) by introducing four types of genes using a retrovirus vector. iPSCs are widely used for research on regenerative medicine and the preparation of disease models to screen new drug candidates. Among the Yamanaka factors, Klf4 and c-Myc are oncogenes, and there is a risk of tumor development if these are integrated into genomic DNA. Therefore, regenerative medicine using mRNA, which poses no risk of genome insertion, has attracted attention. Direct reprogramming and protein supplementation therapy using mRNA encoding the reprogramming genes or the specific proteins have been particularly studied in recent years. However, to apply mRNA to regenerative medicine, the further development of delivery technology that can deliver mRNA to specific tissues is strongly demanded. Thus, with the development of research on mRNA synthesis/delivery technology and the accumulation of application examples demonstrating the potential usefulness of mRNA, it is expected that mRNA will have a big impact on regenerative medicine.