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.

中文翻译：

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囊性纤维化基因疗法的新方法

基因疗法为囊性纤维化提供了巨大的希望，由于在肺中传递足够量的 CFTR 基因和表达持续时间足够长以产生任何效果的挑战，因此从未完全实现。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，利用我们对 CF 和气道上皮生物学知识和理解的增加，出现了新的机会。新技术包括新的病毒和非病毒载体递送方法，以及替代核酸技术，包括用于基因沉默和基因剪接的寡核苷酸和 siRNA 方法，如在 2019 年欧洲 CF 学会基础科学会议上介绍的本综述所述。克罗地亚杜布罗夫尼克）。我们还简要讨论了其他新兴技术，包括快速发展的 mRNA 和 CRISPR 基因编辑。CF 基因疗法的未来前景现在是多种多样的，并且可能比自发现 CF 基因以来的任何时候都更有希望。