Adeno-associated virus transduction machinery

The Adeno-associated virus (AAV) transduction machinery in airway epithelial cells encompasses the complex network of receptors and intracellular pathways utilized by AAV vectors to deliver therapeutic genetic material. A central component of this machinery is the Adeno-associated virus receptor (AAVR, also known as KIAA0319L), a glycosylated transmembrane protein essential for the endocytosis of most AAV serotypes (Pillay et al., 2016). In airway tissues, the efficiency of this machinery is often limited by the apical membrane's low expression of primary attachment factors like heparan sulfate proteoglycans and the presence of a dense mucus barrier (Zhang et al., 2019). Following receptor binding, the machinery facilitates clathrin-mediated endocytosis, endosomal escape, and microtubule-dependent transport to the nucleus (Berry & Asokan, 2016). This system is the fundamental target for pulmonary gene therapies aiming to correct defects in proteins like the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Understanding and bypassing the limitations of this machinery, such as the slow rate of second-strand DNA synthesis, is critical for improving the efficacy of treatments for chronic lung diseases (Grosse et al., 2017).

Other names

Adeno-associated virus entry pathwayAAV infection machineryAAVR-mediated endocytosisAAV intracellular trafficking

Viral vector-mediated gene delivery involving cell surface receptor binding, internalization via endocytosis, endosomal escape, and nuclear translocation of the viral genome.