(Circulation. 1995;91:541-548.)
© 1995 American Heart Association, Inc.
Articles |
Gene Therapy for Cardiovascular Disease
From the Cardiovascular Research Center and Department of Internal Medicine, University of Michigan (Ann Arbor).
Correspondence to Elizabeth G. Nabel, MD, University of Michigan, Cardiovascular Research Center, MSRB III, Rm 7301, 1150 W Medical Center Dr, Ann Arbor, MI 48109-0644.
Key Words: genes • cardiovascular diseases • myocardium
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Introduction |
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The field of cardiovascular gene transfer has developed rapidly during the past 5 years. Important advances have been made in vector development, in vivo gene delivery, and definition of potential therapeutic targets. Despite substantial progress, a number of technical issues need to be addressed before gene therapy is applied safely and broadly to cardiovascular diseases. In this review, major advances in cardiovascular gene transfer are summarized. In addition, technical issues required for translation of preclinical studies of gene transfer into clinical protocols are discussed.
Advances in recombinant DNA technology, including gene transfer, have stimulated hope that this technology can be used to improve the practice of cardiovascular medicine. Applications of this technology that affect the clinical management of patients include the development of new therapeutic products, engineered by the overexpression of genes, such as recombinant tissue-type plasminogen activator. Recombinant DNA technology has also provided techniques that have been used to create animal models of cardiovascular diseases. These models permit definition of the role of specific gene products in the pathogenesis of cardiovascular diseases. Characterization of its molecular basis has led to a more precise definition of diseases and the potential for relevant clinical treatments. The development of molecular genetic interventions to treat cardiovascular diseases depends on technical advances in the development of methods of gene delivery; achievement of long-term, highly efficient, and targeted expression to relevant cells of the cardiovascular system; and design of vectors that are safe for long-term human administration.
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Methods of Gene Delivery |
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The transduction and expression of genes in appropriate
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