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. 2023 May 9;32:773–793. doi: 10.1016/j.omtn.2023.05.005

Figure 6.

Figure 6

ASOs have formulation-dependent brain distribution following i.c.v. injection

(A) TMEM106b mRNA expression levels 14 days post i.c.v. injection as assessed by qRT-PCR. Data were normalized to GAPDH- and saline-treated controls. One-way ANOVA with multiple comparisons Dunnett’s test (saline control), ∗∗p < 0.002, ∗∗∗∗p < 0.0001. (B) Internalized TA2 concentration 14 days post i.c.v. injection as determined by MOL-PCR. (C and D) Representative anti-ASO IHC brain sections of free TA2 (100 μg)- or TA2-GenVoy(1) (25 μg)-treated animals 4 days following i.c.v. injection. (C) Hemibrain sections stained for TA2 (red staining). Scale bars, 2,000 μm. (D) TA2 IHC staining showing ASO accumulation in piriform cortical neurons, endothelial cells, and the choroid plexus (red staining). Scale bars, 20 μm. (E) Representative cryo-SEM images showing subcellular TA2 localization, red arrows, in piriform cortical neurons, endothelial cells, and ciliated ependymal cells 4 days after administration. Scale bars, 1 μm. (F) Representative cryo-SEM images showing TA2 localization in macrophages lining the ventricle 4 days following TA2-GenVoy(1) administration, red circles. Scale bars, 2 μm. For all panels, mean ± SEM are shown and the 100 μg TA2 dose is represented by bold font.