Department of Pharmacology & Therapeutics, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC, 3010, Australia.
Gene Ther. 2019 Sep;26(9):354-362. doi: 10.1038/s41434-019-0092-5. Epub 2019 Jul 12.
Cystic fibrosis (CF) is a life-limiting disease caused by defective or deficient cystic fibrosis transmembrane conductance regulator (CFTR) activity. The recent advent of the FDA-approved CFTR modulator drug ivacaftor, alone or in combination with lumacaftor or tezacaftor, has enabled treatment of the majority of patients suffering from CF. Even before the identification of the CFTR gene, gene therapy was put forward as a viable treatment option for this genetic condition. However, initial enthusiasm has been hampered as CFTR gene delivery to the lungs has proven to be more challenging than expected. This review covers the contemporary clinical and scientific knowledge base for small molecule CFTR modulator drug therapy, gene delivery vectors and CRISPR/Cas9 gene editing and highlights the prospect of these technologies for future treatment options.
囊性纤维化（CF）是一种由缺陷或不足的囊性纤维化跨膜电导调节因子（CFTR）活性引起的危及生命的疾病。最近，美国食品和药物管理局（FDA）批准的 CFTR 调节剂药物伊伐卡托单独或与拉卡法特或替扎法特联合使用，已经能够治疗大多数患有 CF 的患者。即使在 CFTR 基因被发现之前，基因治疗就已经被提出作为这种遗传疾病的一种可行治疗选择。然而，最初的热情受到了阻碍，因为向肺部输送 CFTR 基因被证明比预期更具挑战性。本综述涵盖了小分子 CFTR 调节剂药物治疗、基因传递载体和 CRISPR/Cas9 基因编辑的当代临床和科学知识库，并强调了这些技术在未来治疗选择中的前景。
