ABSTRACT

Introduction: Cystic fibrosis (CF), is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and affects thousands of people throughout the world. Lung disease is the leading cause of death in CF patients. Despite the advances in treatments, the management of CF mainly targets symptoms. Recent CFTR modulators however target common mutations in patients, alleviating symptoms of CF. Unfortunately, there is still no approved treatments for patients with rare mutations to date.

Areas covered: This paper reviews current treatments of CF that mitigate symptoms and target genetic defects. The use of gene and drug delivery systems such as viral or non-viral vectors and nano-compounds to enhance CFTR expression and the activity of antimicrobials against chronic pulmonary infections respectively, will also be discussed.

Expert opinion: Nano-compounds tackle biological barriers to drug delivery and revitalize antimicrobials, anti-inflammatory drugs and even genes delivery to CF patients. Gene therapy and gene editing are of particular interest because they have the potential to directly target genetic defects. Nanoparticles should be formulated to more specifically target epithelial cells, and biofilms. Finally, the development of more potent gene vectors to increase the duration of gene expression and reduce inflammation is a promising strategy to eventually cure CF.

摘要

简介: 囊性纤维化 (CF) 是由囊性纤维化跨膜电导调节剂 (CFTR) 基因突变引起的，影响着全世界成千上万的人。肺病是 CF 患者死亡的主要原因。尽管在治疗方面取得了进步，但 CF 的管理主要针对症状。然而，最近的 CFTR 调节剂针对患者的常见突变，减轻了 CF 的症状。不幸的是，迄今为止，对于具有罕见突变的患者仍然没有批准的治疗方法。

涵盖的领域：本文回顾了减轻症状和针对遗传缺陷的 CF 的当前治疗方法。还将讨论使用基因和药物递送系统（例如病毒或非病毒载体和纳米化合物）来分别增强 CFTR 表达和抗菌剂对慢性肺部感染的活性。

专家意见：纳米化合物解决了药物输送的生物障碍，使抗微生物剂、抗炎药甚至基因输送给 CF 患者重振。基因治疗和基因编辑特别令人感兴趣，因为它们有可能直接针对遗传缺陷。应配制纳米颗粒以更具体地针对上皮细胞和生物膜。最后，开发更有效的基因载体以增加基因表达的持续时间并减少炎症是最终治愈 CF 的有希望的策略。