Klamut Henry J, Chen Shin-Tai, Lau K-H William, Baylink David J
Departments of Medicine and Biochemistry, Loma Linda University and the Musculoskeletal Disease Center (151), Jerry L. Pettis Memorial Veterans Administration Medical Center, 11201 Benton Street, Loma Linda, CA 92357, USA.
Crit Rev Eukaryot Gene Expr. 2004;14(1-2):89-136.
Skeletal gene therapy is an attractive new approach to the treatment of bone disorders. Impressive advances in our knowledge of the molecular genetic basis of skeletal disorders and fracture healing have led to the development of novel therapeutics based on ectopic expression of one or more genes in patient cells that can influence repair or regenerative processes in bone. Although still a relatively immature field, proof-of-principle for enhanced bone formation through skeletal gene therapy has already been established. The challenge now is to more precisely define optimal cellular targets and therapeutic genes, and to develop safe and efficient ways to deliver therapeutic genes to target cells. In this review, we will highlight some of the exciting advances that have been made in skeletal gene therapy in recent years, with a focus on treatment of localized skeletal lesions. Strengths and weaknesses of current approaches will be discussed, as will strategies for improved safety and therapeutic outcome in the future. Skeletal gene therapy can have an enormous impact on patient care. The next 5 years will present us with unparalleled opportunities to develop more effective therapeutic strategies and overcome obstacles presented by current gene transfer technologies.
骨骼基因治疗是一种治疗骨骼疾病的颇具吸引力的新方法。我们对骨骼疾病和骨折愈合的分子遗传基础的认识取得了令人瞩目的进展，这促使人们开发出基于在患者细胞中异位表达一个或多个基因的新型疗法，这些基因能够影响骨骼的修复或再生过程。尽管这仍然是一个相对不成熟的领域，但通过骨骼基因治疗增强骨形成的原理验证已经确立。现在面临的挑战是更精确地确定最佳细胞靶点和治疗基因，并开发出安全有效的方法将治疗基因传递到靶细胞。在这篇综述中，我们将重点介绍近年来骨骼基因治疗取得的一些令人兴奋的进展，尤其关注局部骨骼病变的治疗。我们将讨论当前方法的优缺点，以及未来提高安全性和治疗效果的策略。骨骼基因治疗可能会对患者护理产生巨大影响。未来五年将为我们提供前所未有的机会，以开发更有效的治疗策略并克服当前基因转移技术所带来的障碍。
