Table 4.

Gene Therapy Targets for Arrhythmia

Molecular Target	Stage in Development	Findings	Model Assessed	Reference
KCNH2‐G628S	Preclinical	Prolonged refractory period by shutting down IKr, eliminating arrhythmia inducibility	Pig Dog	Sasano et al, Nat Med, 200610 Amit et al, Circulation, 201087 Soucek et al, Heart Rhythm, 201288
Cardiac sodium channel 4a (SCN4a)	Preclinical	Reduced VT inducibility, increased Vmax causing rapid conduction, and decreased electrogram fragmentation	Dog	Lau et al, Circulation, 200911
Connexin 32	Preclinical	Improved gap junctional conductance but no antiarrhythmic effect and larger infarct size	Dog	Boink et al, J Am Coll Cardiol, 20133
Connexin 40	Preclinical	Enhanced atrial conduction and prevented atrial fibrillation	Pig	Igarashi et al, Circulation, 201233
Connexin 43	Preclinical	Improved conduction and reduced arrhythmia susceptibility	Pig	Greener et al, J Am Coll Cardiol, 201222 Igarashi et al, Circulation, 201233 Bikou et al, Cardiovasc Res, 201189
Sarcoendoplasmic reticulum calcium‐ATPase 2a (SERCA2a)	Preclinical	Reduced VT and VF during reperfusion Reduced premature ventricular contraction and nonsustained VT Decreased APD alternans	Pig Rat Guinea Pig	Prunier et al, Circulation, 200890 Lyon et al, Circ Arrhythm Electrophysiol, 201191 Cutler et al, Circ Arrhythm Electrophysiol, 200992
Adenylyl cyclase 1 (ADCY1)	Preclinical	Increased beating rate, provided stable pacemaker effects	Dog	Boink et al, J Interv Card Electrophysiol, 201193
Adenylyl cyclase 6 (ADCY6)	Preclinical	Provided biological pacing during catecholaminergic stimulation	Pig	Ruhparwar et al, Tissue Eng Part A, 201094
Kir2.1	Preclinical	Increased pacemaking	Guinea Pig	Miake et al, Nature, 2002, J Clin Invest, 200362,95

VT indicates ventricular tachycardia; VF, ventricular fibrillation; APD, action potential duration.