Evans Christopher H, Ghivizzani Steven C, Robbins Paul D
Center for Molecular Orthopaedics, Harvard Medical School, 221 Longwood Avenue, BL1-152, Boston, MA 02025, USA.
Clin Orthop Relat Res. 2004 Dec(429):316-29. doi: 10.1097/01.blo.0000148854.14399.ec.
We review progress in the field of orthopaedic gene therapy since the concept of using gene transfer to address orthopaedic problems was initiated approximately 15 years ago. The original target, arthritis, has been the subject of two successful Phase I clinical trials, and additional human studies are pending in rheumatoid arthritis and osteoarthritis. The repair of damaged musculoskeletal tissues also has proved to be a fruitful area of research, and impressive enhancement of bone healing has been achieved in preclinical models. Rapid progress also is being made in the use of gene transfer to improve cartilage repair, ligament healing, and restoration of various additional tissues, including tendon and meniscus. Other applications include intervertebral disc degeneration, aseptic loosening, osteoporosis, genetic diseases, and orthopaedic tumors. Of these various orthopaedic targets of gene therapy, tissue repair is likely to make the earliest clinical impact because it can be achieved with existing technology. Tissue repair may become one of the earliest clinical successes for gene therapy as a whole. Orthopaedics promises to be a leading discipline for the use of human gene therapy.
自大约15年前提出利用基因转移来解决骨科问题的概念以来，我们回顾了骨科基因治疗领域的进展。最初的目标——关节炎，已经成为两项成功的I期临床试验的主题，并且在类风湿性关节炎和骨关节炎方面还有更多人体研究正在进行中。受损肌肉骨骼组织的修复也已被证明是一个富有成果的研究领域，并且在临床前模型中已经实现了对骨愈合的显著增强。在利用基因转移改善软骨修复、韧带愈合以及包括肌腱和半月板在内的各种其他组织的修复方面也正在取得快速进展。其他应用包括椎间盘退变、无菌性松动、骨质疏松症、遗传疾病和骨科肿瘤。在基因治疗的这些各种骨科靶点中，组织修复可能最早产生临床影响，因为它可以通过现有技术实现。组织修复可能成为整个基因治疗最早取得的临床成功之一。骨科有望成为使用人类基因治疗的领先学科。
