Delayed miR-199a Administration After Myocardial Infarction Precludes Pro-Regenerative Effects.

miR-199a carried by adeno-associated virus serotype 6 (AAV6) proved cardioreparative in a pig model when administered early after myocardial infarction (MI). To test whether the therapeutic efficacy of miR-199a is maintained when its administration is delayed, AAV6-miR-199a or a control AAV6 were injected 1 or 2 weeks after MI. Scar mass and cardiac contractile performance parameters were not significantly different between AAV6-miR-199a-treated and AAV6-control pigs. Nonetheless, most AAV6-miR-199a-treated pigs died from sudden death at 40 to 52 days after vector administration. For clinical translation, it appears mandatory to administer miR-199a early after MI and through modalities other than permanent expression from a viral vector.