Effect of AAV-mediated non-fibrogenic TBX18 expression in mouse hearts

Gene therapy-based biological pacemakers have been proposed as an alternative to their hardware-based counterparts. In this context, short-term ectopic expression of the T-box transcription factor 18 (TBX18) in the ventricle reportedly generated potent short-term pacemaker function in various animal models. Here, we investigated the effect of adeno-associated virus (AAV)-mediated long-term expression of TBX18 in mouse hearts. Mice were injected with AAV vectors containing GFP-labeled Nanoluciferase or GFP-labbeled TBX18 at the left ventricular apex. Left ventricular tissues were harvest 2 weeks later. The results suggest that at non-fibrogenic level, TBX18 expression suppress working myocardial genes but does not induce pacemaker phenotype.