Figure 8.

Histological and western blot analyses show no evidence of cardiotoxicity following systemic injection of the AAVrh7.4.tMCK.hCAPN3 vector

(A) Western blot analysis of cardiac tissue from the HD (6 × 10¹² vg) cohort 20 weeks after systemic injection of the AAVrh7.4.tMCK.hCAPN3 vector showed no detectable CAPN3 protein. A full-length, 94-kDa hCAPN3 band is present in human skeletal muscle as a positive control. (B) mRNA levels of mice corresponding to samples shown in the western blot, represented individually as bar graphs. (C) H&E-stained paraffin sections of the left ventricles from representative heart samples of CAPN3 KO mice 20 weeks after systemic injection of the LD (3 × 10¹² vg) and HD revealed no histopathology, indicating no long-term toxicity. Muscle fiber necrosis, regeneration, or inflammation was not seen. Scale bar, 30 μm in the UT image (applies to all).