Fig. 1

Schematic diagram for the transduction life cycle of AAV virions. A Genome structure of AAV. A single-strand DNA ~ 4.7 kb is flanked by two inverted terminal repeat (ITR). Multiple cap and rep genes are transcribed from two open reading frames through different promoters and alternative splicing. B Surface rendering of the crystal structure of AAV2. The capsid adopts an icosahedral conformation with key structural features including the fivefold channel, threefold protrusion, and the twofold depression. C Model of cellular entry and trafficking of AAV vectors. Following binding to a receptor/co-receptor complex, AAV enters target cell through endocytosis. Virions traverse through the trans-Golgi network including early and late endosomes. The conformation change in capsid exposes the phospholipase A2 (PLA2) domain to enable endosome escape and nuclear import via the nuclear pore complex (NPC). After nuclear import, intact capsids accumulate in the nucleolus followed by genome release in the nucleoplasm. The single-strand DNA is converted to double strand via the ITR and host-cell DNA polymerase. The rep and cap genes are then transcribed, and the new virion particles are assembled. The capsid can be also neutralized or eliminated by the antibody and ubiquitylation-proteasome system within the extracellular and cytosolic space, respectively