•Successful gene transfer could be confirmed.•Expression reached a peak at 7–8 days, followed by a slow decline.•Increased infection and gene delivery with higher titers.•No systemic wash-out was noted in recipients.•Preferred gene expression in cardiomyocytes over other cell types.•Mean allograft survival was significantly prolonged from 9 to 135 days.•There was a synergistic effect on allograft survival when both genes were delivered, potentially due to suppression of T lymphocyte infiltration induced by localized overexpression of Il4 and IL10. Here, IL4 is linked to infection.