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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1414.)
© 2000 American Heart Association, Inc.

Editorials

Adenoviral Vectors and Gene Transfer to the Blood Vessel Wall

Timothy O’Brien

From the Mayo Clinic and Foundation, Rochester, Minn.

Correspondence to Timothy O’Brien, 200 First St SW, Rochester, MN 55905. E-mail obrien.timothy@mayo.edu

Key Words: adenovirus • gene therapy • gene transfer

Gene therapy may be defined as the treatment of human disease via the delivery of genes to human tissues. The transferred gene may replace a defective gene or may introduce a new function to a cell. Alternatively, the transgene may enhance an existing cellular function or manifest this function at a time it would not normally be exhibited. Local delivery of genes to the vascular wall is a promising approach to a number of vascular disorders. Overexpression of therapeutic genes within the vessel wall may avoid side effects associated with systemic delivery of the product and result in higher concentrations locally at the site of disease. Inhibition of restenosis after vascular injury^{1 2 3 4 5} and enhancement of new vessel formation after gene transfer has been demonstrated in numerous animal models.^{6 7 8 9} Phase 1 clinical trials of vascular gene therapy have also recently been reported.^{10 11} Two major obstacles to the clinical application of this technology include limitations of the currently available vectors and difficulties delivering genes to the vessel wall in vivo by percutaneous methods. Although direct gene delivery to a surgically isolated segment of the blood vessel has been demonstrated, efficient percutaneous catheter-mediated delivery to the coronary vasculature is more challenging.¹²

A number of vector systems have been used to deliver genes to the blood vessel wall. The simplest involves the use of plasmid alone or plasmid complexed with liposomes. These methods result in relatively inefficient gene transfer. However, if the therapeutic product is a potent secreted protein, biological effects may be observed . . . [Full Text of this Article]

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