mRNA biotherapeutics landscape for rare genetic disorders

The medical emergency of COVID-19 brought to the forefront mRNA vaccine technology where the mRNA vaccine candidates mRNA-1273 and BNT162b2 displayed superlative and more than 90% efficacy in protecting against SARS-CoV2 infections. Rare genetic disorders are rare individually, but collectively they are common and represent a medical emergency. In mRNA biotherapeutic technology, administration of a therapeutic protein-encoding mRNA-nanoparticle formulation allows for in vivo production of therapeutic proteins to functionally complement the protein functions lacking in rare disease patients. The platform nature of mRNA biotherapeutic technology propels rare disease drug discovery and, owing to the scalable and synthetic nature of mRNA manufacturing, empowers parallel product development using a universal production pipeline. This review focuses on the advantages of mRNA biotherapeutic technology over current therapies for rare diseases and provides summaries for the proof-of-concept preclinical studies performed to demonstrate the potential of mRNA biotherapeutic technology. Apart from preclinical studies, this review also spotlights the clinical trials currently being conducted for mRNA biotherapeutic candidates. Currently, seven mRNA biotherapeutic candidates have entered clinical trials for rare diseases, and of them, 3 candidates entered in the year 2023 alone. The rapid pace of clinical development promises a future where, as with mRNA vaccines for COVID-19, mRNA biotherapeutic technology would combat an emergency of rare genetic disorders.