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Abstract

Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by defective ciliary motility, leading to recurrent respiratory infections and chronic airway damage. Gene therapy holds promise for treating PCD, but its effectiveness in patient-derived models remains uncertain. This study aimed to evaluate the therapeutic potential of lentiviral gene delivery in restoring ciliary function in patient-derived nasal apical-out airway organoids. Using nasal epithelial cells from both healthy individuals and PCD patients with mutations in DNAAF1, DNAAF3, or DNAAF6, we established organoid models to assess gene therapy efficacy. Lentiviral vectors successfully restored the expression and proper localization of DNAAF proteins in mutant organoids, significantly improving ciliary beating frequency and the proportion of organoids with functional cilia. These findings provide proof-of-concept evidence supporting gene therapy as a viable approach to correct ciliary defects in PCD, paving the way for targeted treatments.

Keywords

primary ciliary dyskinesia cilia motility lentiviral gene delivery

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