Fig. 4: In utero base editing improves cardiac function and survival in Idua-W392X mice.

a–d Echocardiographic parameters were measured in 4-month-old B6 (N = 10), Idua-W392X mice prenatally injected with AAV.ABE.Idua (N = 10, except 4-month aortic valve diameter, N = 8), and uninjected Idua-W392X mice (N = 10). Mice that died prior to 6 months of age are denoted with a green X. e–h Echocardiographic parameters were measured in 6-month-old B6 (N = 10), prenatally injected mice (N = 10), and surviving uninjected mice (N = 6). i–l Ascending aorta diameter and representative ultrasounds from 4-month-old B6 (N = 10), prenatally injected mice (N = 10), and uninjected mice (N = 10). Mice that died prior to 6 months of age are denoted with a green X. Scale bar = 1 mm. m–p Ascending aorta diameter and representative ascending aorta ultrasounds from 6-month-old B6 (N = 10), prenatally injected mice (N = 10), and surviving uninjected mice (N = 6). Scale bar =1 mm. q–s Representative Masson’s trichrome stain highlighting collagen deposition in aortic outlets including aortic valve (*), and ascending aorta (black and white arrow) in 6-month-old B6, prenatally injected mice, and uninjected mice. Red stains muscle, pink stains cytoplasm, black stains nuclei, and blue stains collagen. Images constructed with 40x tile stitch. Scale bar = 200 µm. Staining was repeated in five biological replicates per sample. t Six-month survival analysis comparing B6 (N = 10), prenatally injected mice (N = 10), and uninjected mice (N = 10). Wilcoxon test for multiple comparisons used to assess 4 month ascending aorta diameter; Mantel–Cox method used to assess survival; Student’s t-test used for all other comparisons; α = 0.05. All tests two-sided. LV left ventricle, Ao aorta. AAV.ABE indicates AAV.ABE.Idua. Source data are provided as a Source Data file.