Fig. 4: Comparison of Sotorasib and HiFiCas9 therapy. | Nature Communications

Fig. 4: Comparison of Sotorasib and HiFiCas9 therapy.

From: High-fidelity Cas9-mediated targeting of KRAS driver mutations restrains lung cancer in preclinical models

Fig. 4

A Cell viability assay combining HiFiCas9 therapy and Sotorasib in parental H358 cells (n = 3 independent biological replicates). Control/HiFiCas9 infection was performed 24 h before Sotorasib treatment. Data represent the mean ± SD of three independent biological replicates, analyzed using a two-way ANOVA. (AdV-Control vs AdV-HiFiCas9; 0 nM Sotorasib p = 0.0005, 3 nM Sotorasib p = 0.0008, 6 nM Sotorasib p = 0.0056) B Colony formation assay combining HiFiCas9 therapy and Sotorasib in parental H358 cells. C Cell viability of PDXOs treated with HiFiCas9 therapy and/or Sotorasib. Data represent the mean ± SD of three independent biological replicates derived from three different PDXs, analyzed using a two-tailed unpaired t-test. TP79: AdV-HiFiCas9, p = 0,0133, Combo, p = 0.003; TP60: AdV-HiFiCas9, p = 0.0004, Sotorasib, p = 0.0058, Combo, p = 0.04. D Representative images of organoid cultures five days post-treatment with adenovirus control or HiFiCas9. Scale bar = 100 μm. E Cell viability of Sotorasib-resistant cells treated with HiFiCas9 therapy in 2D cultures. Data represent mean ± SEM from N independent biological replicates, analyzed using a two-tailed one-sample t-test (H358R1-R2, n = 4; H23, n = 3). F Cell viability of Sotorasib-resistant cells treated with HiFiCas9 therapy in 3D cultures. Data represent mean ± SEM from N independent biological replicates, analyzed using a two-tailed one-sample t-test (H358-R1, n = 3; H358-R2, n = 4; H23, n = 5, p = 0.0005). G Representative images of 3D cultures of cells ten days post-treatment with Adenovirus control or HiFiCas9. Scale bar = 50 μm. Source data for panels A, C, E and F are provided in the Source Data file.

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