Adenovirus mediated-gene transfer into cardiomyocytes.

To circumvent limitations imposed by conventional gene transfer techniques into cardiac muscle cells, we studied whether replication defective adenovirus would obviate this limitation to basic studies of signal transduction and transcriptional control processes in the heart. We demonstrate here the utility of adenovirus mediated gene transfer to introduce foreign DNA into post-mitotic terminally differentiated ventricular myocytes with uniformity and high efficiency. We also provide evidence for the genetic modification of neonatal ventricular myocytes by adenovirus early region 1 (E1) proteins and their impact on cardiac gene transcription and DNA synthesis respectively. Thus, for studies of transcriptional control processes in the heart, which until now have been restricted to neonatal ventricular myocytes; adenovirus mediated gene transfer provides a means to genetically manipulate adult cardiac muscle cells. The advent of adenovirus gene transfer will extend our understanding of the molecular mechanisms that mediate basic cardiac disease and may ultimately provide a means to therapeutically mitigate the disease process.