Fig. 6: Inhalable antiviral Cas13a mRNA in rodents.

a, Apparatus for mouse studies. b, 100 µg of aNLuc mRNA formulated was delivered to mice at the indicated final mRNA concentration. Lungs were analyzed at 1 d for luminescence as fold change of total flux relative to controls. Bars represent mean ± s.d. (n = 3). One-way ANOVA with multiple comparisons on log-transformed data, where ****P < 0.0001 and *P = 0.0211. c, Mice were infected with 3 LD₅₀ A/WSN/33 as indicated after delivery of 100 µg of aNLuc mRNA. At 1 d after delivery, lungs were analyzed for luminescence. d, Quantification of part c as fold change total flux. Bars represent mean ± s.d. (n = 2). One-way ANOVA with multiple comparisons on log-transformed data, where ***P = 0.0005, **P = 0.001 and *P = 0.0011. e, Infected mice were dosed with Cas13a mRNA with guides at 6 hpi. Weights are plotted as mean ± s.e.m. (n = 5). f, Lung viral loads as mean fold change ± s.d. from the NTCR (n = 5). Unpaired two-tailed t-test on log-transformed data, where **P = 0.0063. g, Apparatus for hamster studies. h, Hamsters were dosed as indicated with aNLuc mRNA. Lungs were analyzed at 1 d for luminescence. i, Quantification of part h as fold change of total flux. Bars represent mean ± s.d. (n = 2). One-way ANOVA with multiple comparisons on log-transformed data, where ****P = 0.0002 and ***P = 0.0004. j, Hamsters were dosed with Cas13a mRNA with guides 20 h before infection with SARS-CoV-2 (n = 12 until day 3 and n = 6 until days 4–6). Lines indicate mean body weight normalized to day 0. Shaded region represents s.e.m. measured per cage. k, Lung viral loads from hamsters at 6 d after infection (n = 4). Data represent mean N copy number ± s.e.m.. Brown–Forsythe and Welch ANOVA with Dunnett’s multiple comparisons on log-transformed data, where **P = 0.0016 and *P = 0.0198.