Treatment of Hereditary Hypertrophic Cardiomyopathy through Cas13-mediated RNA base Editing

Hypertrophic Cardiomyopathy (HCM) is the most common monogenic heart disease, affecting 0.2% to 0.5% of the population (15-20 million), with 50% of cases linked to gene mutations. These mutations lead to increased contractile function and energy consumption in the heart, raising the risk of arrhythmias and heart failure. Over 20 disease-causing mutations have been identified, with the MYH7 gene affecting 25-40% of patients (5-8 million people). However, current treatments like Aficamten and Mavacamten do not prevent disease progression and have notable side effects. Advancements in targeted therapies and gene therapies are emerging. Base editing techniques can correct disease-causing mutations in vivo and in vitro, potentially rescuing disease phenotypes. Unlike CRISPR-Cas DNA editing, RNA editing modifies mRNA, influencing protein production without altering DNA, offering safer, reversible corrections of mutated transcripts. The potential of CRISPR/Cas13-mediated base editing for genetic cardiomyopathy therapy is still being explored.