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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:196-207.)
© 1999 American Heart Association, Inc.

Brief Review

Vascular Gene Transfer

From Bench to Bedside

Iftikhar J. Kullo; Robert D. Simari; Robert S. Schwartz

From the Division of Cardiovascular Diseases and Internal Medicine (I.J.K., R.D.S., R.S.S.), and the Department of Biochemistry and Molecular Biology (R.D.S.), Mayo Clinic and Mayo Foundation, Rochester, Minnesota.

Correspondence to Iftikhar J. Kullo, MD, Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minn 55905.

	Introduction

 
Since the initial experiments nearly a decade ago, remarkable progress has been made in the field of vascular gene transfer, and trials with human subjects already are under way. The potential of vascular wall gene transfer as therapy for various vascular diseases is considerable.^{1 2} The purpose of this review is 2-fold: (1) to delineate the methods and principles underlying vascular gene transfer and (2) to discuss how gene transfer might be used in the treatment of vascular diseases.

	Part I: Basic Principles

 
An overview of the basic principles of vascular gene transfer provides a perspective of its potential for vascular wall gene therapy. In this section, methods of gene transfer to the vascular wall, shortcomings of the available vectors, and techniques of vector delivery to the vascular bed are discussed.

Methods of Gene Transfer to the Vasculature
As a target organ for gene transfer, the vasculature has several unique features (Table 1). The principal methods of introducing genetic material into the vasculature include a cell-based approach, ex vivo gene transfer to vessel segments, and in vivo gene transfer to the vascular wall.

View this table: [in this window] [in a new window]   Table 1. Unique Features of Vasculature as Target Organ for Gene Transfer

Cell-Based Gene Transfer
Cell-based gene transfer requires harvesting vascular wall cells, in vitro transduction, followed by seeding the vessel wall with transduced cells. Although this strategy has several potential applications, it is technically difficult (Table 2). Both of the major vascular wall cell types, the smooth muscle cell (SMC) and the endothelial cell (EC), can be modified genetically for vascular gene transfer.

View this table: [in this window] [in a new window]   Table 2. Cell-Based Vascular Gene Transfer

SMCs
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