En-580-03 suppression and replacement gene therapy for kcnh2-mediated arrhythmias

KCNH2-mediated arrhythmias are caused by either loss-of-function (type 2 long QT syndrome, LQT2) or gain-of-function (type 1 short QT syndrome, SQT1) pathogenic variants in the KCNH2-encoded Kv11.1 potassium channel which is essential for the rapid delayed rectifier current (IKr) that contributes to the cardiac action potential (AP). No current therapies target the molecular cause of either LQT2 or SQT1.