AAV9-EF1a(core)-GFP

The ninth serotype of AAV (AAV9) was first identified in human isolates in 2004 and was named a new serotype because its serological profile differs from previously known AAVs, however, it is thought to be closely related to the clade containing AAV7 and AAV8. AAV9 uses terminal N-linked galactose as a primary receptor and is also thought to bind to putative integrins, as well as LR as a coreceptor. Scalable AAV9 purification protocols have been developed, including ion exchange chromatography and sucrose gradient centrifugation. The capsid of rAAV9 has one of the highest total amounts of post-translational modifications, including multiple ubiquitination, phosphorylation, SUMOylation, and glycosylation modifications, as well as acetylation. AAV9 appears to be able to achieve cell transduction with superior efficiency to other AAVs in most tissues. For example, in a study designed to investigate the distribution of AAV1–9 after systemic administration in a mouse model, AAV9 demonstrated rapid onset of efficacy, optimal genome distribution, and highest protein levels compared to all other AAVs. Furthermore, in the central nervous system of mice, non-human primates, and feline models, it has a unique property compared to other serotypes in that it can cross the blood-brain barrier and transduce not only neurons but also non-neuronal cells, including astrocytes, which are not usually transduced by other AAVs, and also shows a tropism for retinal photoreceptor cells. AAV9-based viral vectors have also been shown to be more efficient than AAV1 and AAV8-based viral vectors (5-10 times more efficient than AAV8 in some cases) for myocardial transduction in mice, non-human primates, and pigs, due to another significant property of AAV9 - its ability to cross the physical barrier of the endothelium of the vascular system. Another example of the superiority of AAV9 over other AAVs was demonstrated in a study by Inagaki K et al., where the serotype achieved stable transduction of mouse hepatocytes, skeletal muscle, and pancreatic cells. AAV9-based viral vectors also appear to have affinity for mouse photoreceptor cells, renal tubular epithelial cells, interstitial cells in testicular interstitial tissue, and alveolar and nasal epithelia.