Tate Stephen, Elborn Stuart
Belfast City Hospital, Department of Respiratory Medicine, Northern Ireland.
Expert Opin Drug Deliv. 2005 Mar;2(2):269-80. doi: 10.1517/17425247.2.2.269.
A decade ago it was widely anticipated that cystic fibrosis would be one of the first diseases to be treated by gene therapy. The difficult hurdle of cloning the responsible gene had been accomplished, its function was established and the lung appeared readily accessible for gene replacement. Since the first clinical trials for cystic fibrosis lung disease in the early 1990s it has become increasingly apparent that successful lung-directed gene therapy is significantly more complex than was first envisioned. Numerous obstacles including vector toxicity, inefficient transgene expression and limited vector production have delayed progress. An increased understanding of vector biology and host interaction has led to the development of novel strategies to enhance the efficiency and selectivity of gene delivery to the lung. Although significant challenges remain, there is now a realistic prospect of a clinically effective treatment in the next 10 years.
十年前，人们普遍预计囊性纤维化将成为首批通过基因疗法治疗的疾病之一。克隆致病基因这一难题已被攻克，其功能得以确定，而且肺部似乎易于进行基因替换。自20世纪90年代初首次针对囊性纤维化肺病进行临床试验以来，越来越明显的是，成功的肺部定向基因疗法比最初设想的要复杂得多。包括载体毒性、转基因表达效率低下和载体产量有限在内的众多障碍延缓了进展。对载体生物学和宿主相互作用的深入了解促使人们开发出了新策略，以提高基因传递至肺部的效率和选择性。尽管重大挑战依然存在，但未来十年实现临床有效治疗现在已有现实的前景。
