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.

COVID-19 的医疗紧急事件将 mRNA 疫苗技术带到了最前沿，其中候选 mRNA 疫苗 mRNA-1273 和 BNT162b2 在预防 SARS-CoV2 感染方面表现出卓越的功效，功效超过 90%。罕见的遗传性疾病单独来看是罕见的，但总的来说它们很常见并且代表医疗紧急情况。在 mRNA 生物治疗技术中，给予编码治疗性蛋白质的 mRNA 纳米颗粒制剂可以在体内产生治疗性蛋白质，以在功能上补充罕见病患者缺乏的蛋白质功能。mRNA 生物治疗技术的平台性质推动了罕见疾病药物的发现，并且由于 mRNA 制造的可扩展性和合成性质，使得能够使用通用生产管道进行并行产品开发。本综述重点介绍了 mRNA 生物治疗技术相对于当前罕见疾病疗法的优势，并总结了为证明 mRNA 生物治疗技术潜力而进行的概念验证临床前研究。除了临床前研究外，本次综述还重点介绍了目前正在进行的 mRNA 生物治疗候选药物的临床试验。目前，已有 7 个 mRNA 生物治疗候选药物进入罕见病临床试验，其中 3 个候选药物仅在 2023 年就进入了临床试验。临床开发的快速发展预示着未来，与 COVID-19 的 mRNA 疫苗一样，mRNA 生物治疗技术将对抗罕见遗传性疾病的紧急情况。