Vascular gene therapy in the 21st century.

The technology of gene transfer has developed rapidly and has been applied successfully as pharmacological therapy in animal models of human vascular disease. Human vascular gene therapy has not become a reality although clinical trials are starting. In the next century, gene therapy will find its place in the vascular physicians' armamentarium as new pharmacological targets are defined and new vectors devised for gene transfer. Vascular gene therapy, the use of gene transfer to treat diseases of the vascular system, excites the imagination and captures the public's attention because it promises at a single step almost magically to cure the previously uncurable. The goal has been elusive although the promise remains. What can we look forward to in the 21st century? Will the dream ever be realized or is it a fantasy that will always be out of reach? The sceptics argue that research into pharmacology continues to provide us with powerful drugs for the treatment of vascular disease. Why bother with gene transfer? Could not the same goals be achieved by more conventional means? These questions demand answers and adequate justification. In developing the response, we gain a clear understanding of the potential of gene therapy and thereby define a better set of objectives. Gene therapy in broad terms covers somatic cell and germ line gene therapy. Genetic manipulation of the germ line leads to the development of transgenic animals with specific genes that have been deleted or overexpressed; these animals are useful for the study of gene function. Their organs might also be of use for transplantation into humans. For example, transgenic pigs are being developed for this purpose(1). Although the study of transgenic animals and the field of germ line gene therapy are of great importance for vascular biology, they will not be covered here. This review will address vascular somatic gene therapy and will attempt to focus on potential targets, progress made in the last decade, and the steps needed to achieve clinical application.