Recent Progress in the Rational Design of mRNA Vaccines.
Messenger RNA (mRNA)-based vaccines, including circular RNA (circRNA) and self-amplifying RNA (saRNA), have emerged as the most transformative platforms, offering tremendous potential in prophylactic and therapeutic medicine, particularly in the prevention of infectious diseases and cancer immunotherapy. Nevertheless, their optimization remains limited by the instability of mRNA, its innate immunogenicity, and low protein expression efficiency in vivo. In recent years, rapid advancements in mRNA sequence design and delivery technologies have improved therapeutic protein production and enhanced vaccine efficacy and safety. This article reviews mRNA-based vaccines, including conventional non-replicating mRNA and emerging approaches such as circRNA and saRNA, with a focus on recent progress, sequence optimization, and delivery systems. Additionally, the article highlights recent advancements in computational technologies for vaccine design. Finally, the article outlines current manufacturing challenges and potential solutions.