ABSTRACT

The ability to introduce genes efficiently into a wide variety o f tissues and cell types in vivo, including those o f the myocardium, has been an intense area o f recent investigation for both basic research purposes and gene therapy (1-5). From a basic science perspective, it has become increasingly apparent that the study o f gene regulation in cultured cells is not always equivalent to that in the intact animal. Because there are no established cardiac myocyte cell lines, and because successful transfection o f adult cardiocytes has not been reported, the majority o f studies o f cardiac gene expression have been performed in primary cultures o f fetal and neonatal cardiocytes. Therefore, the relationship between the developmental stage of the cultured cells and the intact adult cardiocytes must also be brought into question. In addition to facilitating in vivo studies o f cardiac gene expression, the ability to stably overexpress specific gene products in cardiac myocytes in vivo would repre­ sent a powerful tool with which to study the effects o f those gene products on cardiac physiology. Although basic studies o f cardiac gene expression and physiology can be performed in transgenic mice, the generation of transgenic animals is costly and time-consuming (6). For these reasons, studies o f cardiac gene expression and the physiology o f genetically modified cardiac myocytes would be greatly enhanced by a simple and efficient means of in vivo gene transfer. In addition to its usefulness as a basic research tool, in vivo gene transfer into the myocardium might also have important therapeutic im-

plications for a wide variety o f cardiovascular diseases, including acquired and inherited cardiomyopathies as well as coronary artery disease.