Fig. 6: P76 efficiently delivers mRNA and crRNA and prevents SARS-CoV-2 infection in hamsters.
From: Species-agnostic polymeric formulations for inhalable messenger RNA delivery to the lung
a, Nebulized P76 formulations are more efficient than hDD90-118. The quantification of hamster lung luminescence at 24 h post transfection of 1.25 mg kg–1 of Cas13a-NLuc mRNA. The bars represent geometric mean ± s.d. n = 2. **p < 0.01 (one-way ANOVA with Dunnett’s multiple comparisons on log-transformed data) b,c, Nebulized P76 formulations are more efficient than hDD90-118 at delivering RNA cargo of different lengths. Images (b) and fold change total flux (c) of hamster lungs 24 h after delivery of the indicated total dose of Cas13-NLuc mRNA and crRNA. The bars represent geometric mean ± s.d. n = 2. ***p < 0.001 (one-way ANOVA with Šidák’s multiple comparisons on log-transformed data). d–i, P76 delivery of Cas13 mRNA along with N3.2 guide prevents SARS-CoV-2 infection in the hamster model. d, Hamsters were treated with either nebulized P76 or hDD90-118-formulated Cas13 mRNA and crRNA. 20 h later, the hamsters were intranasally inoculated with 103 PFU of WA-1 SARS-CoV-2. The hamsters were euthanized on day 5 and the lungs were extracted and processed for viral load quantification. n = 8 hamsters per group. e, Per-cent normalized hamster weight over time. The symbols and error bars represent mean and per-cent weight ± s.e.m., respectively. f, Per-cent hamster weight at day 5 post infection. The bars represent mean ± s.d. g, Per-cent normalized hamster weight over time. The symbols and error bars represent mean and per-cent weight ± s.e.m., respectively. h, Per-cent hamster weight at day 5 post infection. The bars represent mean ± s.d. i, Per-cent knockdown of SARS-CoV-2 RNA in the lung at day 5 post infection. The bars represent mean ± s.d. *p < 0.05, **p < 0.01, ***p < 0.001 (one-way ANOVA with Dunnett’s multiple comparisons). n = 4–5 per group. All the p values are listed in Supplementary Table 3.
