Figure 5.

Repeated i.v. injections of 0.1 mg/kg or 0.5 mg/kg FAH mRNA-LNPs, or 0.5 mg/kg FAH mRNA-LNPs injected i.m. rescue Fah-deficient mice from death

(A) NTBC supplementation was withdrawn from Fah-deficient mice 5 days before treatment. Blood was collected 1 day before treatment (PB; day −1), at intermediate bleeding time points 24 h after injections (B1–B3 on days 6, 11, and 16), and on day of termination (T; day 21) (n = 5 Fah-deficient mice/condition). (B) Normalized body weights of Fah-deficient mice that were repeatedly injected i.v. (C) Normalized serum SA and (D) TYR levels in Fah-deficient mice repeatedly injected i.v. with the dose of FAH mRNA-LNPs indicated. (E) Survival of Fah-deficient mice repeatedly injected i.m. with the dose of FAH mRNA-LNPs indicated (five mice/group). (F) Normalized body weights of Fah-deficient mice repeatedly injected i.m. with FAH mRNA-LNPs. (G) Normalized serum SA and (H) TYR levels in Fah-deficient mice repeatedly injected i.m. with FAH mRNA-LNPs. Data are the means ± SEM. Significantly different from mice that received a 0.1-mg/kg dose: ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 (two-tailed Student’s t test).