Antisense and gene therapy to prevent restenosis

A primary pathologic response to vascular injury is the proliferation and m igration of vascular smooth muscle cells and the development of neointimal lesions. An increasing body of knowledge regarding the molecular and geneti c basis of neointimal disease has created a unique opportunity for the trea tment of this complex disorder. Gene therapy attempts to correct pathobiolo gical processes by either inhibiting or correcting cellular functions at th e level of gene expression. These endpoints are achieved by the delivery of either functional genes or oligonucleotides, capable of interfering with a cell's programmed machinery. Since the early 1990s, the evolution of this technology, along with an ever-expanding source of pathobiological informat ion, has led to many novel approaches for the treatment of restenosis in ar terial balloon injury as well as vein graft bypass failure. Using a variety of targets, inhibition of proliferation has predominantly been achieved th rough direct disruption of the cell cycle machinery. In addition, others ha ve demonstrated successful inhibition by interfering with the signals for c ellular proliferation or the enhancement of anti-proliferative stimuli. As this exciting therapeutic alternative evolves, improvements in safety, spec ificity and efficiency will enhance the likelihood of widespread clinical a pplication.