uniQure, Meibergdreef 61, 1105 BA Amsterdam, The Netherlands.
Expert Rev Clin Pharmacol. 2014 Jan;7(1):53-65. doi: 10.1586/17512433.2014.852065. Epub 2013 Nov 25.
There has been great interest over the past two decades in developing gene therapies (GTs) to treat a variety of diseases; however, translating research findings into clinical treatments have proved to be a challenge. A major milestone in the development of GT has been achieved with the approval of alipogene tiparvovec (Glybera(®)) in Europe for the treatment of familial lipoprotein lipase deficiency. At this important stage with the evolution of GT into the clinic, this review will examine the safety aspects GT with adeno-associated virus (AAV) vectors. The topics that will be covered include acute reactions, immunological reactions to the AAV capsid and expressed transgene, viral biodistribution and shedding, DNA integration and carcinogenicity. These safety aspects of GT will be discussed with a focus on alipogene tiparvovec, in addition to other AAV vector GT products currently in clinical development.
在过去的二十年中，人们对开发基因疗法（GT）治疗各种疾病产生了浓厚的兴趣；然而，将研究成果转化为临床治疗一直是一个挑战。GT 发展的一个重要里程碑是在欧洲批准了用于治疗家族性脂蛋白脂肪酶缺乏症的 alipogene tiparvovec（Glybera(®)）。在 GT 进入临床的这个重要阶段，本综述将检查腺相关病毒（AAV）载体 GT 的安全性方面。涵盖的主题包括急性反应、对 AAV 衣壳和表达的转基因的免疫反应、病毒的生物分布和脱落、DNA 整合和致癌性。将重点讨论 GT 的这些安全性方面，除了其他正在临床开发中的 AAV 载体 GT 产品外，还将讨论 alipogene tiparvovec。
