Department of Gene Therapy, Imperial College London, Manresa Road, London SW3 6LR, UK.
Proc Am Thorac Soc. 2010 Nov;7(6):408-14. doi: 10.1513/pats.201004-029AW.
The report of the first patients with cystic fibrosis (CF) to receive cystic fibrosis transmembrane conductance regulator gene (CFTR) therapy appeared in 1993, and since then there have been more than 20 clinical trials of both viral and nonviral 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 U.K. Cystic Fibrosis Gene Therapy Consortium is focused on a clinical program to establish whether these proof-of-principle measures translate into clinical benefit. Here, we review the published literature, discuss the limitations to gene therapy in the CF airway, and consider issues influencing the design of clinical trial programs.
1993 年，首例接受囊性纤维化跨膜电导调节因子（CFTR）基因治疗的囊性纤维化（CF）患者的报告发表，此后，已有超过 20 项病毒和非病毒基因转移剂的临床试验。这些试验主要是单次给予鼻腔或下呼吸道，并且是围绕分子或生物电结果测量设计的。尽管钠离子吸收亢进没有得到改善，但已报道转导基因 mRNA 和氯离子分泌的部分纠正。英国囊性纤维化基因治疗联合会专注于临床计划，以确定这些原理验证措施是否转化为临床益处。在这里，我们回顾了已发表的文献，讨论了 CF 气道中基因治疗的局限性，并考虑了影响临床试验设计的问题。
