Avoidance of Immune Response Prolongs Expression of Genes Delivered to the Adult Rat Myocardium by Replication-Defective Adenovirus

Background Gene delivery is a rapidly expanding field with potential applications to every human organ system. Recently, adenoviruses have been used as efficient vectors for in vivo gene transfer into the myocardium. These methods, however, have shown a sharp decline of gene expression after 1 week. To test the hypothesis that an immune-effector mechanism is involved in this decline, we compared the results after injection of adenovirus-5 carrying the β-galactosidase gene (Adβ-gal) into the left ventricular myocardium of athymic nude rats (NDRs) versus immunocompetent Sprague-Dawley rats (SDRs). Methods and Results Adβ-gal (5.0×109 PFU/mL) was injected into the left ventricle of NDRs (n=16) and SDRs (n=22). Hearts were harvested, embedded in paraffin, and sectioned and stained for β-gal activity, hematoxylin and eosin and picrosirius red at 4, 21, 35, 85, and 120 days. Representative samples were immunostained with antibodies directed at inflammatory markers. β-gal activity was quantified by digital plani...