Advancing Protein‐Coding RNA Engineering: From Structural Refinement to Biomedical Implementation

ABSTRACT Messenger RNA (mRNA), emerging as a revolutionary therapeutic tool, has shown remarkable potential in diverse fields such as vaccine development, tumor immunotherapy, gene therapy, and protein replacement therapy, attributed to its high programmability and safety. However, traditional engineered mRNA therapeutics encounter obstacles like short half‐lives and limited protein expression, which impede their extensive application in the biomedical domain. In recent years, with the progress of RNA modification technologies and the advent of novel RNA techniques, including mRNA, self‐amplifying RNA (saRNA), circular RNA (circRNA), and branched RNA (brRNA), researchers have achieved substantial breakthroughs in enhancing RNA stability, prolonging protein expression, and reducing immunogenicity. This article comprehensively reviews the structure, function, optimization strategies, and biomedical applications of these protein‐coding RNAs.