Extended Data Fig. 6: Genomic and proteomic analysis of select tissues following dual AAV9 ABE editing.
From: Base editing correction of hypertrophic cardiomyopathy in human cardiomyocytes and humanized mice
a, Viral copy numbers for the N terminal AAV and C terminal AAV were quantified from the right atrium (RA), right ventricle (RV), left atrium (LA), left ventricle (LV), lung, liver, spleen, and quadriceps muscle (Quad) from ABE-treated Myh6h403/+ mice at 16 weeks of age. b, The percentage of A to G editing was determined by HTS of genomic DNA in the RA, RV, LA, LV, lung, liver, spleen and Quad from ABE-treated and saline-injected Myh6h403/+ mice. c, The percentage decrease in mutant transcripts in the RA, RV, LA, and LV was determined by HTS of cDNA from ABE-treated and saline-injected Myh6h403/+ mice. The percentage decrease was greater in the RV (22.7%, P = 0.0202) and the LV (26.7%, P = 0.00157) compared to the LA (12.9%). d, Cardiac myofibrils were isolated from Myh6WT mice, Myh6h403/+ mice, and ABE-treated Myh6h403/+ mice, run on a 4–20% polyacrylamide gel, and stained with Coomassie G-250. Key sarcomeric proteins are marked, including titin, myosin heavy chain (MHC), myosin binding protein C (MyBP-C), actin, cardiac troponin T (cTnT), cardiac tropomyosin (cTm), and cardiac troponin I (cTnI). Sizes for ladder markings are in kDa. Relative protein amounts for each key sarcomeric protein are normalized to WT. Data are mean ± s.d. *P < 0.05 by Student’s unpaired two-sided t-test, n = 3 male mice for each group.
