Rare genetic diseases, often referred to as orphan diseases due to their low prevalence and limited treatment options, have long posed significant challenges to our medical system. In recent years, Messenger RNA (mRNA) therapy has emerged as a highly promising treatment approach for various diseases caused by genetic mutations. Chemically modified mRNA is introduced into cells using carriers like lipid-based nanoparticles (LNPs), producing functional proteins that compensate for genetic deficiencies. Given the advantages of precise dosing, biocompatibility, transient expression, and minimal risk of genomic integration, mRNA therapies can safely and effectively correct genetic defects in rare diseases and improve symptoms. Currently, dozens of mRNA drugs targeting rare diseases are undergoing clinical trials. This comprehensive review summarizes the progress of mRNA therapy in treating rare genetic diseases. It introduces the development, molecular design, and delivery systems of mRNA therapy, highlighting their research progress in rare genetic diseases based on protein replacement and gene editing. The review also summarizes research progress in various rare disease models and clinical trials. Additionally, it discusses the challenges and future prospects of mRNA therapy. Researchers are encouraged to join this field and collaborate to advance the clinical translation of mRNA therapy, bringing hope to patients with rare genetic diseases.

中文翻译：

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mRNA疗法：开创罕见遗传病治疗的新时代


罕见遗传病由于患病率低且治疗选择有限，通常被称为孤儿病，长期以来对我们的医疗系统构成了重大挑战。近年来，信使RNA（mRNA）疗法已成为治疗由基因突变引起的各种疾病的一种非常有前景的治疗方法。使用脂质纳米颗粒 (LNP) 等载体将经过化学修饰的 mRNA 引入细胞中，产生可补偿遗传缺陷的功能性蛋白质。 mRNA疗法具有剂量精确、生物相容性、瞬时表达和基因组整合风险最小等优点，可以安全有效地纠正罕见疾病的遗传缺陷并改善症状。目前，数十种针对罕见疾病的mRNA药物正在进行临床试验。这篇综合综述总结了 mRNA 疗法在治疗罕见遗传病方面的进展。介绍了mRNA疗法的发展、分子设计和递送系统，重点介绍了基于蛋白质替代和基因编辑的罕见遗传疾病的研究进展。综述还总结了各种罕见病模型和临床试验的研究进展。此外，它还讨论了 mRNA 疗法的挑战和未来前景。鼓励研究人员加入这一领域，合作推进mRNA疗法的临床转化，为罕见遗传病患者带来希望。