mRNA Therapeutics Beyond Infectious Diseases: Expanding Therapeutic Applications and Future Perspectives

Messenger RNA (mRNA) therapeutics have rapidly evolved from experimental nucleic acid constructs into a clinically validated therapeutic platform. Their successful application during the COVID-19 pandemic accelerated interest in broader therapeutic uses beyond infectious diseases.

This review summarizes the expanding therapeutic applications of mRNA technologies, recent technological advances, translational progress, current challenges, and future prospects across diverse medical fields.

A comprehensive review of the published literature was conducted, synthesizing evidence from preclinical investigations, clinical studies, and recent advances in mRNA engineering, delivery systems, and translational research.

Advances in mRNA design, nucleoside modification, codon optimization, and delivery platforms, particularly lipid nanoparticles and emerging organ-targeted carriers, have expanded applications to cancer immunotherapy, personalized vaccines, autoimmune and inflammatory diseases, protein replacement therapy, cardiovascular regeneration, neurological disorders, and rare genetic diseases. Emerging technologies, including self-amplifying and circular RNA systems, further enhance therapeutic potential.

Despite significant progress, challenges remain, including optimization of targeted delivery, long-term safety, repeat-dose tolerability, manufacturing complexity, cold-chain requirements, production costs, and equitable global access. Continued technological innovation and regulatory harmonization are critical for successful clinical translation.

mRNA therapeutics are transitioning from a vaccine-centered technology to a versatile platform for precision medicine. Advances in delivery systems, scalable manufacturing, and artificial intelligence-assisted sequence design are expected to accelerate their integration into the treatment of chronic, genetic, and regenerative diseases.