Advancing mRNA therapeutics from design to delivery.

Abstract

mRNA therapeutics have emerged as a transformative platform for vaccines and protein replacement therapies, yet their broader clinical and commercial translation remains constrained by challenges in product stability, safety, potency, and delivery efficiency. This review provides a comprehensive overview of the current state of mRNA therapeutic development across the entire product lifecycle, spanning RNA design, manufacturing process optimization and characterization, scale-up and continuous manufacturing, lipid nanoparticle design, formulation, and delivery. Unlike prior reviews that focus on individual stages, we present an end-to-end perspective linking drug substance and drug product development, with emphasis on technological advances over the past 5 years. By integrating these advances, this review offers a practical roadmap for overcoming key bottlenecks and accelerating next-generation mRNA therapeutics.