PO-02-244 AAV6-MEDIATED GFP GENE TRANSFER INDUCES TACHYARRHYTHMIAS IN A PORCINE MODEL OF AV BLOCK

Green fluorescent protein (GFP) is a reporter widely utilized to evaluate gene transfer efficiency and used as control in therapeutic overexpression strategies. Although it frequently considered be an innocuous protein, there also evidence indicating interference with contractile function electrophysiological properties, potentially leading cardiac dilation functional deterioration. Cognizant of these possible limitations, we GFP provide valuable starting point local its potential deleterious effects. To pro-arrhythmic effects porcine model complete atrioventricular block (CAVB). A total eight pigs were implanted pacemaker, after which radiofrequency ablation CAVB was generated. Four weeks induction the animals received catheter-based intramyocardial injections saline, AAV6-CMV-GFP or not injected at all. All then observed for four more weeks. Monitoring included weekly pacemaker interrogations. Ventricular arrhythmias assessed by means increase maximum heart rates dependency. post-ablation all displayed maximal 75 ± 16,9 bpm notably increased AAV6-CMV-GFP-injected two post-treatment (240 10 bpm; Figure A), but (n = 5, 78 29,5 A). Electronically paced beats showed remarkable reduction transduced post-injection (40 37,36 %; B). commonly studies, our experiments reveal occurrence ventricular treatment. Mechanistically, could triggered tissue damage stemming from inflammatory response exacerbated reaction capsid transgene. As result, locally should transgene large animal studies validate therapies.