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Fig. 7 | Genome Biology

Fig. 7

From: Antisense suppression of the nonsense mediated decay factor Upf3b as a potential treatment for diseases caused by nonsense mutations

Fig. 7

Combination treatment of Upf3b-ASO and read-through agents results in production of full-length hFIX protein and improved coagulation activity in hFIX-R29X mice. hFIX-R29X mice aged 8–14 weeks (n = 5–6, 2–3 female and 3 male mice per group) were treated every five days with six total doses of DPBS, Control-GalNAc-ASO (Control G-ASO, 15 mg/kg) Upf3b-GalNAc-ASO (Upf3b G-ASO, 10 mg/kg), Gspt1-GalNAc-ASO (Gspt1 G-ASO, 5 mg/kg), or a combination of Upf3b-GalNAc-ASO (Upf3b G-ASO, 10 mg/kg) and Gspt1-GalNAc-ASO (Gspt1 G-ASO, 5 mg/kg). Geneticin (28 mg/kg) was administered daily during the final seven days of the study either alone, in combination with Upf3b-GalNAc-ASO treatment, Gspt1-GalNac-ASO treatment, or in combination with Upf3b- and Gspt1-GalNAc-ASOs as described. Animals were sacrificed 48 h after the last dose of ASO and 9 h after the last dose of geneticin. Untreated KO and hFIX-WT mice were used as controls. Results are presented as means ± standard errors. a Upf3b, b Gspt1, and c hFIX mRNA levels were analyzed by qPCR from mouse liver total RNA samples. Gapdh was used as an endogenous control. The expression levels in hFIX-WT mouse liver were set as 1. d Mouse plasma hFIX protein levels as measure by ELISA. e APTT FIX activity assay in plasma from treated male mice (n = 3). Data were normalized using a standard curve generated with pooled WT C57BL6/J mouse plasma. Statistical significance was determined using either a one-way ANOVA (a, b, e) or a two-way ANOVA (c, d) and Dunnett’s multiple comparison test in Prism. All groups were compared to DPBS-treated hFIX-R29X mouse group. * p < 0.05; ** p < 0.01; **** p < 0.0001

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