Figure 6.

In vivo efficacy of multiple dosing of hOTC-mRNA/LNP in OTCD model mice

We monitored body weight (BW) and survival of male Otc^spf-ash mice, which were repeatedly treated with hOTC-mRNA/LNP. Mice were intravenously injected with hOTC-mRNA/LNP (0.3 or 1.0 mg/kg) or saline on days 0, 7, 14, 21, and 28. After the first injection on day 0, mice were provided a high-protein (40%/kcal) diet ad libitum. The experimental scheme is illustrated 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 among the three groups from days 1 to 5. Data were analyzed by two-way ANOVA (F_4,58 = 9.939, p < 0.0001 for time; F_2,58 = 47.74, p < 0.0001 for treatment; F_8,58 = 2.601, p = 0.0168 for interaction), followed by Tukey’s multiple comparisons test. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001. Values are expressed as means ± SD with individual values. (D) Kaplan-Meier survival curves of the three groups. ∗p < 0.05; ∗∗p < 0.01 by log-rank test. n = 5 per group.