Figure 5.

Specificity and tolerability of AAV-S1K treatment in vivo

(A) AAV-S1K treatment is highly specific as determined by strand-specific mRNA-seq. Volcano plot shows differential gene expression of AS mice 5 weeks after AAV-S1K treatment (n = 4) with AAV-mCherry-treated AS mice as controls (n = 3). p values were adjusted by Benjamini-Hochberg correction (p_adj). AAV-S1K-treated mice show no global transcriptomic changes. Red dots indicate genes that were significantly differentially expressed (p_adj < 0.05). Gray dots represent genes without significant difference. (B) Volcano plot shows genes differentially expressed between AS (n = 3) and WT (n = 3) mice. Red dots indicate genes that were significantly different (fold change >1.5, p_adj < 0.05). (C) Normalized expression levels (TPM) for immune-response genes were obtained from RNA-seq analysis. AS mice treated with AAV-S1K or control (AAV-mCherry) and WT mice treated with control (AAV-mCherry) were compared with untreated WT mice (n ≥ 2, mean is indicated, one-way ANOVA with Dunnett’s multiple comparisons test). (D) Normalized expression of Gfap and Iba-1 (TPM) evaluates neuroinflammatory response by the presence of astrocyte or microglia markers (GFAP or IBA1) (n ≥ 2, mean is indicated, Dunnett’s multiple comparisons test, ∗p = 0.02).