KCNH2 gene therapy for Type 1 short QT syndrome

AAV9-mediated KCNH2 suppression-replacement gene therapy in a transgenic rabbit model of type 1 short QT syndrome

European Heart Journal 

Type 1 short QT syndrome (SQT1) is a rare genetic channelopathy affecting (among others) the potassium channel KCNH2 and carries a high risk for lethal arrhythmias in otherwise often healthy individuals with currently limited treatment options.

In this study, KCNH2-specific suppression-and-replacement (KCNH2-SupRep) gene therapy is employed to correct the pathologic phenotype in a transgenic rabbit model of SQT1. Since the genetic strategy suppresses the expression of the variant KCNH2 gene while at the same time, inducing expression of a wildtype KCNH2 gene, this study serves as a proof-of-concept for gene therapy not only of SQT1, but also the more common long QT syndrome where also the KCNH2 gene can be affected. To explore the mechanistic details and electrophysiological findings, read the full study.