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. T

o explore the mechanistic details and electrophysiological findings, read the full study.