University of Edinburgh, Centre for Genomic and Experimental Medicine, University of Edinburgh and Institute of Genetics & Molecular Medicine, Western General Hospital, Edinburgh UK; UK Cystic Fibrosis Gene Therapy Consortium, UK.
Antisense Drug Discovery, Ionis Pharmaceuticals, Carlsbad, California, USA.
J Cyst Fibros. 2020 Mar;19 Suppl 1:S54-S59. doi: 10.1016/j.jcf.2019.12.012. Epub 2020 Jan 13.
Gene therapy offers great promise for cystic fibrosis which has never been quite fulfilled due to the challenges of delivering sufficient amounts of the CFTR gene and expression persistence for a sufficient period of time in the lungs to have any effect. Initial trials explored both viral and non-viral vectors but failed to achieve a significant breakthrough. However, in recent years, new opportunities have emerged that exploit our increased knowledge and understanding of the biology of CF and the airway epithelium. New technologies include new viral and non-viral vector approaches to delivery, but also alternative nucleic acid technologies including oligonucleotides and siRNA approaches for gene silencing and gene splicing, described in this review, as presented at the 2019 annual European CF Society Basic Science meeting (Dubrovnik, Croatia). We also briefly discuss other emerging technologies including mRNA and CRISPR gene editing that are advancing rapidly. The future prospects for genetic therapies for CF are now diverse and more promising probably than any time since the discovery of the CF gene.
基因治疗为囊性纤维化带来了巨大的希望，但由于在肺部中递送足够量的 CFTR 基因和表达持久性以产生任何效果的挑战，这种希望从未完全实现。最初的试验探索了病毒和非病毒载体，但未能取得重大突破。然而，近年来，出现了新的机会，利用我们对 CF 和气道上皮细胞生物学的增加的知识和理解。新技术包括新的病毒和非病毒载体传递方法，但也包括替代核酸技术，包括寡核苷酸和 siRNA 方法用于基因沉默和基因剪接，本综述中介绍了在 2019 年年度欧洲囊性纤维化学会基础科学会议（克罗地亚杜布罗夫尼克）上提出的方法。我们还简要讨论了其他新兴技术，包括 mRNA 和 CRISPR 基因编辑，这些技术正在迅速发展。CF 的基因治疗的未来前景现在多种多样，比 CF 基因发现以来的任何时候都更有希望。
