Fig. S2.

Knockdown of Myh6 with Cas9 results in cardiac failure and hypertrophy. No overt cardiac abnormalities were observed in animals that (i) received AAV-sgRNA against Myh6 only; (ii) were Cas9+ only; or (iii) were both Cas9+ and received AAV-sgRNA against Luciferase, confirming that there is no detectable toxicity associated with either Cas9 or AAV in the heart. In contrast, animals that were Cas9+ and received AAV-sgRNA against Myh6 displayed massive cardiac enlargement characteristic of heart failure. Tissues were isolated 12 wk after AAV delivery. Fibrosis, as assessed by Masson’s trichrome stain (Right), was observed only when both Cas9 and AAV-sgRNA against Myh6 were present. (Scale bar, 40 μm.)