Myocardial infarction creates a critical time window for AAV gene therapy

Recombinant adeno-associated virus (AAV) is a major gene delivery vector for cardiac gene therapy. The factors that influence AAV-based cardiac gene transfer remain incompletely understood. This study showed that myocardial infarction (MI) enhanced cardiac AAV transduction and gene expression in mice after systemic administration, peaking at the third day post MI. These additional AAV vectors enriched at the infarcted region, correlated with the pathological permeabilization of the coronary vessels. The outcome of AAV-base gene therapy for MI, via Camk2d base editing, was significantly improved when AAV was injected at the third day post MI. Together, our findings uncovered a critical therapeutic time window after MI that facilitated AAV-based cardiac gene transfer, which could be harnessed to boost both basic and translational cardiology.