Beyond the vaccine baseline: Optimizing mRNA stability and translation via regulatory element engineering

The global deployment of messenger RNA (mRNA) vaccines against COVID-19 constituted a pivotal milestone in the history of RNA-based medicine. These achievements were built upon decades of foundational research that demonstrated three critical capabilities: first, the efficient encapsulation of large mRNA transcripts within lipid nanoparticles (LNPs) to facilitate cellular uptake and protect them against extracellular RNases; second, the proof of concept that exogenous mRNA injected into skeletal muscle can successfully hijack host translational machinery to produce functional proteins; and third, the strategic use of modified nucleosides, such as methylpseudouridine, to suppress the innate immune system’s recognition of synthetic RNA through Toll-like receptor 7 and 8 (TLR7 and TLR8) pathways.