Fig. 4: Single i.v. dose of hG6PC S298C mRNA-LNP restores euglycemia, as well as serum and hepatic biomarkers in L.G6pc−/− mice. | Nature Communications

Fig. 4: Single i.v. dose of hG6PC S298C mRNA-LNP restores euglycemia, as well as serum and hepatic biomarkers in L.G6pc−/− mice.

From: mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease

Fig. 4

a Blood glucose levels following administration of hG6PC S298C mRNA-LNP in L.G6pc−/− mice. WT, wild-type mice. (WT treated with PBS, n = 8 per group; L.G6pc−/− treated with eGFP, n = 6, 5, 5, and 5 per group for fasting duration of 0, 2.5, 6, and 24 h, respectively; L.G6pc−/− treated with hG6PC S298C at 0.2 mg/kg, n = 7 per group for all time points; L.G6pc−/− treated with hG6PC S298C at 0.5 mg/kg, n = 7, 6, 6, and 6 per group for fasting duration of 0, 2.5, 6, and 24 h, respectively; L.G6pc−/− treated with hG6PC S298C at 1.0 mg/kg, n = 7 per group for all time points). Data were presented as mean ± SD. b Liver morphology (left panel) and liver weight (right panel) following administration of hG6PC S298C mRNA in L.G6pc−/− mice. Representative liver images are shown from n = 8, 5, 7, 6, and 6 mice per group from WT treated with PBS, L.G6pc−/− treated with eGFP, and L.G6pc−/− treated with hG6PC S298C mRNA at 0.2, 0.5, or 1.0 mg/kg, respectively. c hG6Pase-α S298C protein expression and enzymatic activity in livers of L.G6pc−/− mice. d Hepatic biomarker analysis following administration of hG6PC S298C mRNA-LNP in L.G6pc−/− mice. Liver G6P (left panel), liver glycogen (middle panel), liver triglycerides (right panel). e Serum triglycerides following administration of hG6PC S298C mRNA-LNP in L.G6pc−/− mice. hG6PC S298C mRNA-LNP dose range: 0.2, 0.5, and 1.0 mg/kg. For b–e, quantitative data were presented as mean ± SD (n = 8, 5, 7, 6, and 6 mice per group for WT treated with PBS, L.G6pc−/− treated with eGFP, and L.G6pc−/− treated hG6PC S298C mRNA at 0.2, 0.5, or 1.0 mg/kg, respectively). For statistical analysis, raw values were Log2 transformed and subjected to one-way ANOVA, followed by the Dunnett’s multiple comparisons test, compared to the eGFP mRNA treated group. Statistically significant P values (p ≤ 0.05) are shown in the graphs. Source data are provided as a Source Data File.

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