Fig. 6: A single injection of Cbh-ABE9-dual-AAV9 and Ksp-ABE9-dual-AAV9 extends lifespan of Pkd1RC/null mice.
From: In vivo base editing rescues ADPKD in a humanized mouse model
a Statistic analysis of body weights and KW/BW ratios of Pkd1RC/null mice treated with 1 × 1012 vg of Cbh-ABE9-dual-AAV9, Ksp-ABE9-dual-AAV9 and vehicle (n = 10), p = 0.43 of body weight calculated by one-way ANOVA test of age matched mice. The KW/BW ratio was calculated at the endpoint of Pkd1RC/null mice died at different days. b The survival rate of Pkd1RC/null mice treated with Cbh-ABE9-dual-AAV9 (1 × 1012 vg) (n = 10) lived to a mean age of 33.4 ± 1.6 days (p < 0.0001) compared with vehicle treatment (n = 10) (22 ± 3 days), and Pkd1RC/null mice treated with Ksp-ABE9-dual-AAV9 (1 × 1012 vg) lived to a mean age of 37.1 ± 5.9 days (n = 10) (p < 0.05) compared with Cbh-ABE9-dual-AAV9 treatment. c–f Representative kidneys (c), cystic index (d), KW/BW ratios (e) and BUN levels (f) in 20-days-old Pkd1RC/null mice treated with 1 × 1012 vg of Cbh-ABE9-dual-AAV9 and Ksp-ABE9-dual-AAV9 as well as vehicle (n = 10, equal numbers of male and female mice in each group). The colors in the graphs represent female (pink) and male mice (blue). Scale bar, 1 mm. g The comparison of the editing efficiency (%) of the targeted pathogenic variant R3277C in kidneys from Pkd1RC/null mice treated with 1 × 1012 vg of Cbh-ABE9-dual-AAV9 and Ksp-ABE9-dual-AAV9 at PN20 (n = 3 independent replicates). h PC1 protein in kidneys from PN20 Pkd1RC/null mice treated with Cbh-ABE9-dual-AAV9,Ksp-ABE9-dual-AAV9 and vehicle (n = 3 independent replicates). Values and error bars reflect mean ± SD from indicated counts of independent experiments, ns: p > 0.05, *p  <  0.05, **p  <  0.01, ***p  <  0.001, and ****p  <  0.0001 or as indicated in the figure, using two-tailed t-test. Source data are provided as a Source Data file.
