Figure 5.
In vivo efficacy of single dosing of hOTC-mRNA/LNP in OTCD model mice
We monitored body weight (BW), survival, and blood NH3 concentrations of male Otcspf-ash mice treated with hOTC-mRNA/LNP. Mice were administered an intravenous bolus of hOTC-mRNA/LNP at 3.0 mg/kg on day 0. After the injection, mice were provided a high-protein (40%/kcal) diet ad libitum. Untreated mice were used as controls. Blood was sampled from the cheek vein for NH3 determination on days −1, 3, 7, 10, 14, 17, and 21. The experimental scheme is shown in (A). (B) Time course changes of BW of individual mice (% of those on day 0). The dotted line indicates 100%. (C) Comparison of BW changes between the untreated and hOTC-mRNA/LNP-treated groups from days 1 to 5. Data were analyzed by two-way ANOVA (F4,78 = 9.684, p < 0.0001 for time; F1,78 = 341.5, p < 0.0001 for diet; F4,78 = 8.732, p < 0.0001 for interaction), followed by Šídák’s multiple comparisons test. ∗∗p < 0.01; ∗∗∗∗p < 0.0001. Values are expressed as means ± SD with individual values. (D) Kaplan-Meier survival curves of the untreated and hOTC-mRNA/LNP-treated groups. ∗∗∗ p < 0.001 by log-rank test. (E) Comparison of blood NH3 concentrations between the untreated and hOTC-mRNA/LNP-treated groups from days −1 to 10. ∗∗p < 0.01 by Mann-Whitney U test. n = 6 per group. Values are expressed as means ± SD with individual values.