Fig. 5: Cardiac restoration of wild-type MYBPC3 protein levels. | Nature Communications

Fig. 5: Cardiac restoration of wild-type MYBPC3 protein levels.

From: AAV9-mediated MYBPC3 gene therapy with optimized expression cassette enhances cardiac function and survival in MYBPC3 cardiomyopathy models

Fig. 5

Homozygous mice were dosed retro-orbitally IV with vehicle or the indicated doses (vg/kg) of AAV9:mMybpc3, and cardiac protein analyzed two weeks and six weeks post-injection. Restoration of WT levels of cardiac MYBPC3 protein upon dosing Mybpc3-/- mice at two weeks of age with 3E13 and 1E14 vg/kg based upon a immunoblot and b ELISA. c Mybpc3 transgene RNA two weeks and six weeks post-injection. WT (n = 3; 1 M/2 F), Mybpc3-/- Veh (n = 2; 2 F), Mybpc3-/- 3E13 vg/kg (n = 3; 1 M/2 F) and Mybpc3-/- 1E14 vg/kg (n = 3; 1 M/2 F). d Immunohistochemistry for MYBPC3 4 weeks post-injection. Homozygous mice were dosed retro-orbitally IV with vehicle or the indicated doses (vg/kg) of AAV9:mMybpc3 at two weeks of age. WT littermates were harvested, and samples processed simultaneously (n = 2/condition; 10× scale bars: 2 mm; 40× scale bars: 25 µm). e Confocal images for assessment of sarcomere structure in animals six weeks following viral dosing (n = 4/condition, 90× scale bars: 25 µm). f Adult WT male mice were dosed retro-orbitally IV with vehicle or the indicated doses (vg/kg) of AAV9:mMybpc3 and cardiac transgene expression was analyzed 10 weeks post-injection by qPCR for Mybpc3 RNA (normalized to Gapdh). Protein assessment in WT mice was performed by ELISA with equivalent total protein for each sample, as well as g immunoblot; Vehicle, Veh (n = 6), 3E13 vg/kg (n = 5) and 3E14 vg/kg (n = 6). P-value per one-way ANOVA with Tukey’s multiple comparisons test. Data are shown as means ± SEM. Source data are provided as a Source Data file.

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