Fig. 6: Selective AAVR expression in a neuronal subpopulation targets AAV transduction to specific regions in the brain upon systemic delivery.

a, Schematic of the experiment. Mice were injected with AAV-PHP.eB-GFP, a capsid variant that can enter the brain after systemic injection. Brains were extracted after 28 d, and sections were cut on the sagittal plain and nuclear staining was performed. Similar results were seen in two biological replicates; data for male mice are shown, at 6–8 weeks of age. b, Fluorescence microscopy in brain slices of a control mouse. Widespread transduction to different areas in the brain slice was detected (GFP; green). c, Fluorescence microscopy in brain slices of a SELECTIV-KO-Chat mice, which was bred to express AAVR in cholinergic neurons with concomitant KO in all other cell types. Transduction was observed in localized areas, which correspond to areas enriched in cholinergic neurons (GFP; green). d, Higher-magnification images of the brain slices. The AAVR-mCh expression (red) can be seen in the areas with a high density of cholinergic neurons such as the pons and medulla in the SELECTIV-KO-Chat mice. This correlates with high levels of transduction in these areas, while only moderate transduction was seen in control mice. In areas with low levels of Chat-positive cholinergic neurons, such as cerebral cortex, hippocampus and anterior olfactory nucleus, control mice have clear transduction, while SELECTIV-KO-Chat mice show little to no transduction. Scale bars, 1 mm (b,c) and 50 µm (d).