Hortelano G, Chang P L
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Artif Cells Blood Substit Immobil Biotechnol. 2000 Jan;28(1):1-24. doi: 10.3109/10731190009119782.
Hemophilia A and B are X-linked genetic disorders caused by deficiency of the coagulation factors VIII and IX, respectively. Because of the health hazards and costs of current product replacement therapy, much effort is devoted to the development of gene therapy for these disorders. Approaches to gene therapy for the hemophilias include: ex vivo gene therapy in which cells from the intended recipients are explanted, genetically modified to secrete Factor VIII or IX, and reimplanted into the donor; in vivo gene therapy in which Factor VIII or IX encoding vectors are directly injected into the recipient; and non-autologous gene therapy in which universal cell lines engineered to secrete Factor VIII or IX are enclosed in immuno-protective devices before implantation into recipients. Research into these approaches is aided by the many murine and canine models available. While problems of achieving high and sustained levels of factor delivery, and issues related to efficacy, safety and cost are still to be resolved, progress in gene therapy for the hemophilias has been encouraging and is likely to reach human clinical trial in the foreseeable future.
甲型血友病和乙型血友病是分别由凝血因子 VIII 和 IX 缺乏引起的 X 连锁遗传病。由于目前产品替代疗法存在健康风险和成本问题，人们致力于开发针对这些疾病的基因疗法。血友病基因治疗的方法包括：体外基因治疗，即从预期接受者身上取出细胞，进行基因改造以分泌因子 VIII 或 IX，然后重新植入供体；体内基因治疗，即将编码因子 VIII 或 IX 的载体直接注入接受者体内；以及非自体基因治疗，即经基因工程改造能分泌因子 VIII 或 IX 的通用细胞系在植入接受者之前被置于免疫保护装置中。现有许多小鼠和犬类模型有助于对这些方法的研究。虽然实现高且持续的因子递送水平的问题以及与疗效、安全性和成本相关的问题仍有待解决，但血友病基因治疗已取得令人鼓舞的进展，并且在可预见的未来可能进入人体临床试验。
