Cas13-mediated RNA base editing rescues cardiac function in a humanized mouse model of hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease, affecting 0.2% to 0.5% of the population (15-20 million individuals). The most characteristic feature of HCM is the unusual thickening of the left ventricle, typically affecting the interventricular septum. The disease has strong genetic underpinnings, with ~40% of cases attributed to pathogenic variants in cardiac sarcomeric genes.Clinical implications of HCM include a hypercontractile systole and impaired diastolic function, which often precede hypertrophy development. Other potential complications include arrhythmias and sudden cardiac death.Currently, several established therapies substantially improve patient outcomes, including septal myectomy, alcohol septal ablation, and myosin inhibitors such as mavacamten.However, these approaches not address the underlying pathological mechanisms of HCM. Base editing has emerged as a promising technique for correcting and potentially curing genetically based diseases.