AAV9-mutant cMyBPC

AAV9-mutant cMyBPC is an adeno-associated virus serotype 9 (AAV9) gene therapy designed to treat heart failure by delivering a custom-engineered version of the cardiac myosin binding protein C (cMyBPC) gene (MYBPC3). Developed by researchers at Case Western Reserve University, this therapy utilizes a mutant cMyBPC with targeted modifications in the M-domain that mimic the protein's phosphorylated state. Unlike traditional gene replacement therapies for genetic cardiomyopathies, this approach aims to address non-genetic heart failure by directly enhancing sarcomere function. In preclinical mouse models, the therapy demonstrated a dual mechanism of action, providing both inotropic (increased contractility) and lusitropic (accelerated relaxation) effects, thereby improving ejection fraction and diastolic filling.