Fig. 6: Enhanced exposure and biodistribution of ATV^TfR in cynomolgus monkey brain and spinal cord.

a Schematic of the in vivo experimental design. Immunofluorescence images of 3D reconstructed hemibrains (1x objective) (b, c), coronal slice view of hemibrain (200 μm thick, 1x objective) (d, e), and cortical slice view of temporal lobe (ventral cortex) (200 μm thick, 4x objective) (f, g) from cynomolgus monkeys dosed with 23 mg/kg AF647-conjugated control IgG or ATV^TfR (IV) for 2 days. Arrow heads in (f) highlight localization of control IgG to large penetrating vessels, while arrow heads in (g) highlight localization of ATV^TfR within large vessels as well as capillaries. Experiment conducted once with from n = 1/group. Mean fluorescence intensity of ATV^TfR and control IgG in vessels (h) and non-vessels (i) of cynomolgus monkey brains across regions of different depths from surface of the brain. j Mean fluorescence intensity of ATV^TfR and control IgG within vessels of different radii in the cynomolgus monkey brains. k Mean fluorescence intensity of ATV^TfR and control IgG across different brain regions in cynomolgus monkeys. 3D Immunofluorescence images of spinal cords from cynomolgus monkeys dosed with AF647-conjugated control IgG (l) or ATV^TfR (m). Immunostaining image from n = 1/group.