Abstract
Synthetic mRNA has been considered as an emerging biotherapeutic agent for the past decades. Recently, the SARS-CoV-2 pandemic has led to the first clinical use of synthetic mRNA. mRNA vaccines showed far surpassing influences on the public as compared to other vaccine platforms such as viral vector vaccines and recombinant protein vaccines. It allowed rapid development and production of vaccines that have never been achieved in history. Synthetic mRNA, called in vitro transcribed (IVT) mRNA, is the key component of mRNA vaccines. It has several advantages over conventional gene-expressing systems such as plasmid DNA and viral vectors. It can translate proteins in the cytoplasm by structurally resembling natural mRNA and exhibit various protein expression patterns depending on how it is engineered. Another advantage is that synthetic mRNA enables fast, scalable, and cost-effective production. Therefore, starting with the mRNA vaccine, synthetic mRNA is now in the spotlight as a promising new drug development agent. In this review, we will summarize the latest IVT mRNA technology such as new mRNA structures or large-scale production. In addition, the nature of the innate immunogenicity of IVT mRNA will be discussed along with its roles in the development of vaccines. Finally, the principles of the mRNA vaccine and the future direction of synthetic mRNA will be provided.