AAV-mediated gene transfer to cardiac cells in a heterotopic rat heart transplantation model.

ABSTRACT

INTRODUCTION: Adeno-associated virus (AAV) vectors offer the possibility to transfer genes to a wide range of organ and cell types. To determine the efficiency of AAV-mediated gene transfer to cardiac cells, vectors were administered to the heart under various conditions. METHODS: In Sprague-Dawley rats, AAV vectors based on serotype 2 and coding for beta-galactosidase were injected via coronaries into hypothermic nonbeating and normothermic beating hearts before transplantation. In addition, vectors were injected intravenously or into the thigh muscle. After 28 days all animals were humanely killed and organs explanted for analysis. RESULTS: Transgenic DNA was always detectable in the liver and the heart, irrespective of the application mode. However, transgenic mRNA could not be determined in the transplanted hearts. In contrast, direct injection into the thigh muscle resulted in transgenic mRNA production and marker gene expression. After systemic application, transgenic mRNA was detected in the liver but not in the heart. CONCLUSION: The results of our study indicated that AAV-mediated gene transfer to cardiac cells is possible. However, it was impossible to detect transgenic mRNA or marker gene expression in the transplanted hearts after intracoronary perfusion or systemic injection.