Brimble Mark A, Reiss Ulrike M, Nathwani Amit C, Davidoff Andrew M
a Department of Haematology , University College London Cancer Institute , London WC1E 6DD , UK.
b Department of Surgery , St Jude Children's Research Hospital , Memphis , TN 38105 , USA.
Expert Opin Biol Ther. 2016;16(1):79-92. doi: 10.1517/14712598.2015.1106475. Epub 2015 Nov 2.
Hemophilia B is a sex linked, monogenic, coagulation disorder caused by a deficiency in functional factor IX protein. Gene therapy for this disorder via systemic administration of an adeno-associated virus (AAV) encoding an optimized factor IX construct has shown considerable success, ameliorating the bleeding phenotype in a number of patients. However challenges to sustained curative gene transfer in this patient population remain, and as such there are efforts in the field to improve long term factor IX expression, via optimisations to the AAV vector, transgene cassette and correction strategy.
In this article we review the current state of AAV mediated gene therapy for hemophilia B in the clinic, detail progress since the first successful trial, and discuss alternative approaches from the AAV gene therapy field.
AAV mediated gene therapy for hemophilia B is safe and efficacious; however, to achieve gene therapy success on a global scale, improvements to large scale production and alternative AAV serotype approaches need to be designed. With the current means of AAV gene therapy treatment entering the market concomitantly with the advent of long half-life clotting factor products, the quality of life for hemophilia patients worldwide is likely to improve significantly.
血友病B是一种X连锁单基因凝血障碍疾病，由功能性凝血因子IX蛋白缺乏引起。通过全身给药携带优化的凝血因子IX构建体的腺相关病毒（AAV）对该疾病进行基因治疗已取得显著成功，改善了许多患者的出血表型。然而，在这一患者群体中实现持续治愈性基因转移仍面临挑战，因此该领域正在努力通过优化AAV载体、转基因盒和校正策略来提高凝血因子IX的长期表达。
在本文中，我们回顾了AAV介导的血友病B基因治疗在临床上的现状，详述了自首次成功试验以来的进展，并讨论了AAV基因治疗领域的替代方法。
AAV介导的血友病B基因治疗安全有效；然而，为了在全球范围内实现基因治疗的成功，需要设计大规模生产的改进方法和替代AAV血清型方法。随着当前AAV基因治疗手段与长效凝血因子产品的出现同时进入市场，全球血友病患者的生活质量可能会显著提高。
