Li Xinyu, Shen Leyao, Deng Zhenghan, Huang Zeyu
Department of Orthopaedic Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, USA.
Precis Clin Med. 2023 May 30;6(2):pbad014. doi: 10.1093/pcmedi/pbad014. eCollection 2023 Jun.
Osteoarthritis is a complex degenerative disease that affects the entire joint tissue. Currently, non-surgical treatments for osteoarthritis focus on relieving pain. While end-stage osteoarthritis can be treated with arthroplasty, the health and financial costs associated with surgery have forced the search for alternative non-surgical treatments to delay the progression of osteoarthritis and promote cartilage repair. Unlike traditional treatment, the gene therapy approach allows for long-lasting expression of therapeutic proteins at specific sites. In this review, we summarize the history of gene therapy in osteoarthritis, outlining the common expression vectors (non-viral, viral), the genes delivered (transcription factors, growth factors, inflammation-associated cytokines, non-coding RNAs) and the mode of gene delivery (direct delivery, indirect delivery). We highlight the application and development prospects of the gene editing technology CRISPR/Cas9 in osteoarthritis. Finally, we identify the current problems and possible solutions in the clinical translation of gene therapy for osteoarthritis.
骨关节炎是一种影响整个关节组织的复杂退行性疾病。目前，骨关节炎的非手术治疗主要集中在缓解疼痛。虽然终末期骨关节炎可以通过关节成形术治疗，但与手术相关的健康和经济成本促使人们寻找替代的非手术治疗方法，以延缓骨关节炎的进展并促进软骨修复。与传统治疗不同，基因治疗方法允许治疗性蛋白质在特定部位长期表达。在这篇综述中，我们总结了骨关节炎基因治疗的历史，概述了常见的表达载体（非病毒、病毒）、递送的基因（转录因子、生长因子、炎症相关细胞因子、非编码RNA）以及基因递送模式（直接递送、间接递送）。我们强调了基因编辑技术CRISPR/Cas9在骨关节炎中的应用和发展前景。最后，我们确定了骨关节炎基因治疗临床转化中目前存在的问题和可能的解决方案。
