Dynein axonemal intermediate chain 1 (DNAI1) (DNAI1)

Dynein axonemal intermediate chain 1 (DNAI1) is a structural protein that serves as a core component of the outer dynein arm (ODA) complex in motile cilia and flagella (UniProt: Q9UI46). It acts as a scaffold for the assembly of the dynein motor complex, which is essential for the rhythmic beating of cilia required for mucociliary clearance in the respiratory tract and sperm motility (NCBI Gene: 27019). Mutations in the DNAI1 gene are a well-established cause of Primary Ciliary Dyskinesia (PCD), a rare genetic disorder characterized by chronic respiratory infections, bronchiectasis, and situs inversus (OMIM: 604366). Because PCD caused by DNAI1 mutations results from a loss-of-function, the protein is a primary target for genetic medicine, including mRNA-based therapies and viral-mediated gene replacement (PubMed: 32658615). Current therapeutic strategies, such as those being developed by ReCode Therapeutics, focus on delivering functional copies of the DNAI1 transcript to respiratory epithelial cells to restore ciliary function (ClinicalTrials.gov: NCT05816967). These interventions aim to address the root cause of the disease rather than just managing symptoms like chronic infection.

Other names

CILD1DIC1ICS1Dynein intermediate chain 1, axonemalAxonemal dynein intermediate chain 1

Restoration of functional DNAI1 protein expression via exogenous mRNA delivery or viral-mediated gene transfer to re-establish outer dynein arm assembly and ciliary motility.