Fig. 6: Postexposure treatment with LNP-CasRx-pre-gCtsl reduces virus burden in lungs of SARS-Cov-2 infected K18-hACE2 mice.
From: Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection
a, Schematic illustration of the experimental design. Female and male mice were intranasally infected with 105 PFU of SARS-CoV-2. They were treated with LNP-CasRx-pre-gControl or LNP-CasRx-pre-gCtsl through the retro-orbital injections 2 h and 1 DPI. The LNP-CasRx-pre-gControl group consisted of four mice (two females and two males), whereas the LNP-CasRx-pre-gCtsl group had six mice (three females and three males). The lungs were collected at 3 DPI for analysis. b, Representative images for viral N protein immunostaining in lung. One lung section per mouse was subjected to IHC analysis and only one image from each group was shown. Nonvirus, one female and one male mouse. Scale bar, 100 μm. c, Western blot (WB) of viral N protein and Ctsl protein in lung. All mice were subjected to this analysis. Each lane represents an individual mouse. Calnexin was used as a loading control. The ratio of N or Ctsl protein over calnexin is listed under the blot. d, Ctsl transcript levels as normalized by Gapdh. The bar represents the average of the group, while each circle represents an individual animal. P values were calculated by one-tailed Mann–Whitney U-test, grand mean. **P < 0.01. e, Representative photomicrographs of H&E-stained lung sections demonstrating that alveolar septal areas have essentially normal cellularity following LNP-CasRx-pre-gCtsl treatment. One lung section per animal was used for histological analysis and one image from each group was shown. Annotations: thin arrow, inflammatory infiltrate in interstitial regions causing hypercellularity. Scale bars, 100 μm.
