Extended Data Fig. 3: Characterization of the peripheral tropism of AAV-BI30.

AAV-BI30:CAG-NLS-GFP-miR122-WPRE was intravenously administered to adult C57BL/6 mice at 1 × 10¹¹ vg/animal and transduction was assessed after three weeks. Representative images of AAV-BI30 transduction throughout the periphery; high-zoom colocalization of GFP with endothelial markers is shown in the rightmost column. With the notable exception of lung, AAV-BI30 rarely transduced endothelial cells in the microvasculature of peripheral organs – a striking contrast to efficient transduction seen throughout the CNS vasculature. Note residual NLS-GFP expression in hepatocytes of the liver persisting in the presence of miR122 repeats in the viral genome, illustrating AAV-BI30’s potent transduction of this cell type. Transduction observed in kidney glomeruli was non-endothelial; GFP⁺ cells are most likely mesangial cells. Relatively strong endothelial transduction in the interlobular vessels of the renal medulla and the aorta suggest that AAV-BI30 may achieve transduction of large-diameter arteries and veins throughout the systemic circulation. Scale bars are as follows: 100 μm in fourth column from left, 15 μm in rightmost column, and 25 μm in aorta panel. Images are representative of n = 3 animals.