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REVIEW

Lipid nanoparticle-based gene therapies for osteoarthritis: A review

Jie Li1,2 ,  Jing Wang1,2* ,  Qinghao Zhang3,4*
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1 The State Key Laboratory of Bioreactor Engineering, Department of Material Science and Engineering, East China University of Science and Technology, Shanghai, China
2 Department of Material Science and Engineering, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, China
3 Department of Systems Biology, Innovative Center of RNA Medicine, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China
4 Guangming Advanced Research Institute, Southern University of Science and Technology, Shenzhen, Guangdong, China
BMT, 136 https://doi.org/10.12336/bmt.25.00136
Submitted: 6 August 2025 | Revised: 2 October 2025 | Accepted: 9 October 2025 | Published: 9 December 2025
© 2025 by the Author(s). Licensee Biomaterials Translational, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 (CC BY-NC-SA 4.0) (https://creativecommons.org/licenses/by-nc-sa/4.0/deed.en)
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Abstract

Osteoarthritis (OA) remains a leading cause of disability and lacks approved disease-modifying pharmacotherapies, affecting over 500 million people worldwide. Over the past decade, advances in joint biology, molecular research on cartilage and subchondral bone degeneration, and nanomaterial studies for targeted delivery have driven gene therapy strategies for OA. Early clinical studies employing local delivery of anti-inflammatory or anabolic transgenes through adeno-associated virus, helper-dependent adenovirus, or plasmids have demonstrated intra-articular expression and initial safety, establishing regulatory and translational pathways. Recent advances in molecular biology and nanotechnology have enabled the emergence of RNA-based therapies delivered via lipid nanoparticles (LNPs). LNPs, clinically validated through their use in mRNA COVID-19 vaccines, offer a modular and scalable system for nucleic acid delivery. They provide stability for RNA constructs, enhance joint retention, and facilitate penetration into the dense extracellular matrix of cartilage. Preclinical studies have demonstrated that intra-articular administration of LNP-encapsulated small interfering RNAs and messenger RNAs can suppress inflammatory mediators, silence catabolic enzymes, and promote cartilage regeneration. This review summarizes recent studies on the design, optimization, and translational progress of LNP-based RNA therapies for OA, addressing ongoing challenges related to durability, re-dosing, scalability, and immunogenicity. It outlines a roadmap for achieving disease-modifying RNA therapeutics in OA.

Keywords
Osteoarthritis
Gene therapy
Lipid nanoparticle
Gene delivery
Funding
This work was supported in part by the Key Program of the National Natural Science Foundation of China (No. 32230059) and Key Research and Development Plan of Shandong Province (2023CXPT103).
Conflict of interest
The authors declare that they have no conflicts of interest.
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