Nathwani Amit C, Davidoff Andrew M, Tuddenham Edward G D
Department of Academic Haematology, UCL Cancer Institute, Katharine Dormandy Haemophilia and Thrombosis Centre, Rowland Hill Street, London NW3 2PF, United Kingdom; National Health Service Blood and Transplant, Oak House, Reeds Crescent, Watford, Hertfordshire, WD24 4QN, United Kingdom.
Department of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Place Memphis, TN 38105-3678, USA.
Hematol Oncol Clin North Am. 2017 Oct;31(5):853-868. doi: 10.1016/j.hoc.2017.06.011.
The best currently available treatments for hemophilia A and B (factor VIII or factor IX deficiency, respectively) require frequent intravenous infusion of highly expensive proteins that have short half-lives. Factor levels follow a saw-tooth pattern that is seldom in the normal range and falls so low that breakthrough bleeding occurs. Most hemophiliacs worldwide do not have access to even this level of care. In stark contrast, gene therapy holds out the hope of a cure by inducing continuous endogenous expression of factor VIII or factor IX following transfer of a functional gene to replace the hemophilic patient's own defective gene.
目前治疗甲型和乙型血友病(分别为凝血因子 VIII 或 IX 缺乏症)的最佳方法需要频繁静脉输注半衰期短且价格昂贵的蛋白质。凝血因子水平呈锯齿状波动,很少处于正常范围,且会降至很低水平,从而引发突破性出血。全球大多数血友病患者甚至无法获得这种治疗水平。与之形成鲜明对比的是,基因疗法有望通过将功能性基因导入血友病患者体内以替代其自身有缺陷的基因,从而诱导凝血因子 VIII 或 IX 的持续内源性表达,实现治愈。