Table 1: Gene Therapy Targets and Strategies for Ablation of Atrial Fibrillation.

Study	Type of Strategy	Transgene or Target	Findings	Species	Vector	Delivery Method
Rhythm Control
Kikuchi et al. 200533	Reentry-disrupting interventions by prolongation of APD	Human KCNH2-G628S	Atrial APD prolongation. No ventricular effects. Arrhythmia suppression not tested.	Swine	Ad	Epicardial painting
			Atrial APD prolongation eliminated burst pacing-induced AF	Swine	Ad	Epicardial painting
Amit et al.201063		Canine		Swine	Ad	Myocardial injection and electroporation
Soucek et al.201246		KCNH2-G627S
Igarashi et al. 201264	Reentry-disrupting interventions by improvement of atrial conduction velocity	GJA1, GJA5	Improved atrial conduction and prevented AF	Swine	Ad	Epicardial painting
Bikou et al. 201134		GJA1		Swine	Ad	Myocardial injection and electroporation
Liu et al. 200873		HDAC class I and II inhibitor	HDAC inhibition reduced atrial arrhythmia inducibility and atrial fibrosis	Transgenic mice	NA
Trappe et al. 201347		CASP3 inhibitor	Knockdown of caspase 3 suppressed or delayed sustained AF by reducing atrial cardiomyocyte apoptosis	Swine	Ad	Myocardial injection and electroporation
Li et al. 201276 and 201493	Trigger-disruption by preventing Ca2+ leak from SR	CAMK2D inhibitor	Inhibition of CaMKII phosphorylation of RyR2 prevented AF induction	Transgenic mice		NA
Rate Control
Donahue et al. 200031	Modification of AV node of AV node	GNAI2	Suppressed AV conduction and reduced ventricular rate by 20 % in anesthetised animals	Swine	Ad	Intracoronary perfusion and catheterisation
Bauer et al. 200480		GNAI2-Q205L	Suppressed AV conduction and reduced ventricular rate ~20 % in alert animals	Swine	Ad	Intracoronary perfusion and catheterisation
Lugenbiel et al. 201282	Modification of SA node	GNAS siRNA	Suppression of Gαs protein expression reduced ventricular rate by 8–17 % during SR	Swine	Ad	Myocardial injection and electroporation,
Murata et al. 200481	Suppress L-type Calcium channel	GEM	Gem gene transfer to AV node reduced the heart rate by 20 % during AF	Swine	Ad	Intracoronary catheterisation

AF = atrial fibrillation; SR = sinus rhythm, Ad = Adenovirus; AV = atrioventricular; APD = action potential duration; NA = not available.