Extended Data Fig. 4: Validation of a dual AAV9 ABE system in mice.
From: Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice
a, Injection details for treating Myh6h403/h403 mice with ABE-AAV9 or saline. b, Kaplan-Meier curve for Myh6WT mice (n = 7; 4 male, 3 female), Myh6h403/+ mice (n = 8; 2 male, 6 female), Myh6h403/h403 mice (n = 6; 1 male, 5 female), and ABE-treated Myh6h403/h403 mice at a low (AAV LOW, n = 3; 1 male, 2 female) or high dose (AAV HIGH, n = 5; 4 male, 1 female). Median lifespans: Myh6WT and Myh6h403/+ mice, >40 days; Myh6h403/h403 mice, 7 days; AAV LOW Myh6h403/h403 mice, 9 days (1.3-fold longer, P = 0.0201); AAV HIGH Myh6h403/h403 mice, 15 days (2.1-fold longer, P = 0.0014). *P < 0.05, **P < 0.01 by log-rank (Mantel–Cox) test for AAV LOW Myh6h403/h403 mice and AAV HIGH Myh6h403/h403 mice, each, compared to Myh6h403/h403 mice. c, Sanger sequencing chromatograms for a Myh6h403/h403 mouse and a AAV HIGH Myh6h403/h403 mouse showing 35% on-target editing of the target pathogenic adenine at the cDNA level. d, Four-chamber sectioning and Masson’s trichrome staining of a AAV HIGH Myh6h403/h403 male mouse at 15 days of age. No other replications were possible as all other pups (5 total) were cannibalized before hearts could be collected.
