Messenger RNA therapy in bone and joint diseases: Rationale, delivery systems, and applications.

Authors

Yuting Shen, Jiaying Xiong, Yuchen Zhang, Zhifei Gao, Changhai Ding, Yao Lu

Published in

Biomaterials translational. Volume 7. Issue 2. Pages 246-274. Epub Jun 25, 2025.

Abstract

Bone and joint diseases, including bone fractures, osteoarthritis, and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. Conservative therapy and surgical treatment do not always achieve satisfactory outcomes in orthopedics, especially for degenerative bone and joint diseases. Messenger RNA (mRNA) therapy refers to the production of functional proteins and peptides by introducing mRNA into the body. The success of mRNA vaccines during the COVID-19 pandemic highlights the unique advantages of mRNA therapy, including biocompatibility, avoidance of genomic integration, and flexible, sustained delivery. These features make mRNA therapy a versatile therapeutic modality for the treatment of orthopedic diseases. In this review, we first provide an overview of the latest advances in mRNA therapy. We introduce structural modifications of mRNA and advanced gene-editing technologies, including modifications to nucleosides, mRNA domains, and codon sequences. We then discuss the development of mRNA delivery systems, such as nanomaterials, biomimetic carriers, and hydrogels, which enhance mRNA stability, reduce immunogenicity, and improve targeted delivery. This review also explores the application of mRNA therapy in orthopedic diseases, with a particular focus on its utilization in treating bone tumors and degenerative disorders. Despite promising developments, several challenges remain, including optimizing delivery efficiency, prolonging protein expression, and addressing tissue-specific barriers. Accordingly, the current limitations and future directions of mRNA therapy in orthopedic applications are emphasized. In conclusion, mRNA therapy holds great promise and may open new avenues for the treatment of orthopedic diseases and related fields.

PMID:
42760938
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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