Department of Gene Therapy, Faculty of Medicine at the National Heart and Lung Institute, Imperial College London, Manresa Road, London SW3 6LR, UK.
Expert Rev Respir Med. 2009 Aug;3(4):363-71. doi: 10.1586/ers.09.25.
Cystic fibrosis (CF) is a single-gene disorder with insufficient treatment options and a target organ, the lung that is relatively easily accessible. Thus, it is not surprising that in the early years of gene therapy, CF was at the forefront of this field. Since cloning of the CF gene in 1989, 25 Phase I/II clinical trials involving approximately 420 CF patients have been carried out using a variety of viral and nonviral gene transfer agents. Most early trials focused on the nasal epithelium as a surrogate for the lung to allow for easy access and sampling, and, importantly, to ensure safety. Once an acceptable safety profile had been established, gene transfer agents were administered directly into the lung. Although many of these trials established proof-of-principle for gene transfer in the airways, a gene therapy-based treatment has not yet been developed. Here, we will summarize the key findings of these clinical studies and describe current preclinical and clinical research aimed at further developing gene therapy for CF.
囊性纤维化（CF）是一种单基因疾病，治疗选择有限，且靶器官肺部相对容易接近。因此，在基因治疗的早期，CF 处于该领域的前沿也就不足为奇了。自 1989 年 CF 基因被克隆以来，已经进行了 25 项涉及大约 420 名 CF 患者的 I/II 期临床试验，使用了多种病毒和非病毒基因转移剂。大多数早期试验都集中在鼻上皮作为肺部的替代物，以便于进入和采样，而且，重要的是，确保安全性。一旦建立了可接受的安全性概况，就将基因转移剂直接施用于肺部。尽管这些试验中的许多试验都证明了气道中的基因转移是可行的，但尚未开发出基于基因治疗的方法。在这里，我们将总结这些临床研究的关键发现，并描述目前旨在进一步开发 CF 基因治疗的临床前和临床研究。
