Dynein axonemal heavy chain 5 (DNAH5) (DNAH5)

Dynein axonemal heavy chain 5 (DNAH5) is a large motor protein that serves as a critical component of the outer dynein arm (ODA) in motile cilia and flagella. It functions as an ATPase, providing the mechanical force necessary for the rhythmic beating of cilia, which is essential for the mucociliary clearance of pathogens and debris from the respiratory tract [1, 2]. Mutations in the DNAH5 gene are the most frequent cause of Primary Ciliary Dyskinesia (PCD), a genetic disorder characterized by impaired ciliary motion, chronic respiratory infections, and bronchiectasis [2]. Because the DNAH5 gene is exceptionally large, traditional viral-mediated gene therapy is limited by packaging capacity; consequently, mRNA-mediated protein replacement has emerged as a promising therapeutic strategy [3]. This approach involves the delivery of synthetic mRNA encoding functional DNAH5 into airway epithelial cells, typically via lipid nanoparticles, to restore ODA assembly and ciliary function [3, 4]. By re-establishing normal ciliary beat patterns, this therapy aims to improve lung function and reduce the frequency of pulmonary exacerbations in patients with PCD.

Other names

HL1PCDCILD3DNAH9LDynein heavy chain 5, axonemal

mRNA-mediated protein replacement therapy to restore functional DNAH5 protein expression in the ciliary axoneme