Davies Jane C, Alton Eric W F W
Department of Gene Therapy, Imperial College London, SW3 6LR, London, UK.
Methods Mol Biol. 2011;741:55-68. doi: 10.1007/978-1-61779-117-8_5.
The report of the first CF patients to receive CFTR gene therapy appeared in 1993; since then, there have been over 20 clinical trials of both viral and non-viral gene transfer agents. These have largely been single dose to either nose or lower airway and have been designed around molecular or bioelectrical outcome measures. Both transgene mRNA and partial correction of chloride secretion have been reported, although sodium hyperabsorption has not been improved. The UK CF Gene Therapy Consortium is focussed on a clinical programme to establish whether these proof-of-principle measures translate into clinical benefit. Here, we discuss the considerations in designing such a programme, focusing in particular on our choice of the optimal, currently available delivery method and established and novel outcome measures. We highlight the logistic and regulatory complexities of such a clinical programme and finally, we look to the future and consider possible alternative strategies.
首例接受囊性纤维化跨膜传导调节因子（CFTR）基因治疗的囊性纤维化（CF）患者的报告于1993年发表；从那时起，已经有超过20项关于病毒和非病毒基因转移剂的临床试验。这些试验大多是对鼻腔或下呼吸道进行单剂量给药，并且是围绕分子或生物电结果指标设计的。尽管钠超吸收没有得到改善，但已报道了转基因mRNA和氯化物分泌的部分纠正情况。英国CF基因治疗联盟专注于一项临床计划，以确定这些原理验证措施是否能转化为临床益处。在此，我们讨论设计这样一个计划时的考虑因素，特别关注我们对目前可用的最佳给药方法以及既定和新颖结果指标的选择。我们强调了这样一个临床计划在后勤和监管方面的复杂性，最后，我们展望未来并考虑可能的替代策略。
