Cell-surface integrins and co-receptors for AAV2.5T capsid entry

AAV2.5T is a chimeric adeno-associated virus (AAV) capsid, specifically an AAV2/AAV5 hybrid containing a single point mutation (A581T), developed through directed evolution to enhance gene delivery to the human airway epithelium (HAE). The entry of AAV2.5T into target cells is a multi-step process initiated by primary attachment to cell-surface alpha2,3 N-linked sialic acid residues, which serve as the primary attachment factor and are required for internalization. Following attachment, the virus utilizes co-receptors for internalization; while the adeno-associated virus receptor (AAVR, encoded by KIAA0319L) is a universal receptor for most AAVs and is critical for AAV2.5T transduction efficiency, its internalization in polarized airway cells is notably AAVR-independent, suggesting the involvement of an as-yet-unidentified apical co-receptor or specific integrins. Recent studies have also identified WDR63 as a critical host factor for AAV2.5T transduction, although it is not involved in the internalization step itself. This capsid is the delivery vehicle for SP-101, a gene therapy candidate currently in clinical trials for cystic fibrosis, designed to restore CFTR function in the lungs by overcoming the apical entry barriers typical of natural AAV serotypes.

Other names

AAV2.5T entry receptorsAAV2.5T co-receptorsSialic acid and apical entry factors for AAV2.5TAAV2.5T receptor complex

Viral vector-mediated gene delivery via receptor-mediated endocytosis