Tolerability of repeated doses of hOTC-mRNA/LNP in wild-type mice
Female BALB/c mice were injected intravenously with hOTC-mRNA/LNP or Fluc-mRNA/LNP at 0.3 or 1.0 mg/kg, or saline on days 0, 7, and 14, and blood was collected by cardiac puncture from fed mice on day 15. The experimental scheme is shown in (A). (B) Body weight changes from days −1 to 15. Mice were weighed on days −1, 0, 1, 2, 5, 7, 8, 9, 12, 14, and 15 under fed conditions. On days, 0, 7, and 14, mice were weighed before the injection. Data were analyzed by two-way ANOVA (F3.599,53.99 = 55.46, p < 0.0001 for time; F4,15 = 0.3356, p = 0.8490 for treatment; F40,150 = 0.8583, p = 0.7081 for interaction), followed by Dunnett’s multiple comparisons test. Values show means ± SD. (C) Plasma alanine aminotransferase (ALT) levels. Data were analyzed by Kruskal-Wallis test, followed by Dunn’s multiple comparisons test. There was no significant difference between any groups. Data show means ± SD with individual values. n = 4 per group.