Spirovant Sciences, Inc., Philadelphia, Pennsylvania, USA.
Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
Hum Gene Ther. 2023 Sep;34(17-18):821-835. doi: 10.1089/hum.2023.102.
Primary ciliary dyskinesia (PCD) is a genetic disease characterized by defects in motile cilia, which play an important role in several organ systems. Lung disease is a hallmark of PCD, given the essential role of cilia in airway surface defense. Diagnosis of PCD is complicated due to its reliance on complex tests that are not utilized by every clinic and also its phenotypic overlap with several other respiratory diseases. Nonetheless, PCD is increasingly being recognized as more common than once thought. The disease is genetically complex, with several genes reported to be associated with PCD. There is no cure for PCD, but gene therapy remains a promising therapeutic strategy. In this review, we provide an overview of the clinical symptoms, diagnosis, genetics, and current treatment regimens for PCD. We also describe PCD model systems and discuss the therapeutic potential of different gene therapeutics for targeting the intended cellular target, the ciliated cells of the airway.
原发性纤毛运动障碍（PCD）是一种遗传性疾病，其特征是运动纤毛缺陷，而这些纤毛在多个器官系统中起着重要作用。由于纤毛在气道表面防御中起着至关重要的作用，因此肺部疾病是 PCD 的一个标志。由于其依赖于并非每个诊所都使用的复杂测试，并且与其他几种呼吸系统疾病具有表型重叠，因此 PCD 的诊断较为复杂。尽管如此，PCD 的发病率却比以往认为的要高。该疾病的遗传非常复杂，已有多个基因被报道与 PCD 相关。目前尚无治愈 PCD 的方法，但基因治疗仍然是一种很有前途的治疗策略。在这篇综述中，我们概述了 PCD 的临床症状、诊断、遗传学和当前的治疗方案。我们还描述了 PCD 模型系统，并讨论了不同基因治疗针对预期的细胞靶点——气道的纤毛细胞的治疗潜力。
