Abstract

Messenger RNA (mRNA) has shown tremendous potential in disease prevention and therapy. The clinical application requires mRNA with enhanced stability and high translation efficiency, ensuring it not to be degraded by nuclease and to target to specific tissues and cells. The mRNA immunogenicity can be reduced by nucleotide modification, and its translation efficiency can be enhanced by codon optimization. The 5´ capping structure and 3´ poly A increase mRNA stability, and the addition of 5' and 3' non-translational region regulates mRNA translation initiation and protein production. A nanoparticle delivery system protects mRNA from degradation by ubiquitous nuclease, enhances its circulation concentration and assists it entrancing cytoplasm for the purpose of treatment and prevention. In this article, we review the recent advances of mRNA technology, discuss the methods and principles to enhance mRNA stability and translation efficiency; summarize the requirements involved in designing mRNA delivery systems with the potential of industrial translation and biomedical application. Furthermore, we provide insights into future directions of mRNA therapeutics to meet the need for personalized precision medicine.

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