Concise Review: Application of Chemically Modified mRNA in Cell Fate Conversion and Tissue Engineering

Chemically modified RNA (cmRNA) has potential as a safe and efficient tool for nucleic acid‐based therapies and regenerative medicine. Modifications in the chemistry of mRNA can enhance stability, reduce immunogenicity, and thus facilitate mRNA‐based nucleic acid therapy, which eliminates risk of insertional mutagenesis. In addition to these valuable advantages, the mRNA‐based method showed significantly higher efficacy for reprogramming somatic cells to pluripotency compared with DNA‐ or protein‐based methods. These findings suggest cmRNA can provide a powerful and safe tool for cell programming and reprogramming. Delivery methods, particularly using lipid nanoparticles, provide strategies for cell and organ‐specific targeting. The present study comprehensively compares studies that have used cmRNAs for cell fate conversion and tissue engineering. The information should be useful for investigators looking to choose the most efficient and straightforward cmRNA‐based strategy and protocol for tissue engineering and regenerative medicine research. Stem Cells Translational Medicine 2019;8:833&843 Chemically modified RNA can be used for reprogramming (dedifferentiation) somatic cells to stem cells or directed differentiation of stem cells to a desired cell type. Somatic cells can also be directly reprogrammed (trans‐differentiation) whereas therapeutic mRNAs may facilitate tissue regeneration.