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J Thorac Cardiovasc Surg 2003;125:994-997
© 2003 The American Association for Thoracic Surgery

Editorials

Gene therapy in cardiac surgery: Is there a role?

Frank W. Sellke, MD

From Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.

Received for publication Aug 15, 2002. Accepted for publication Aug 19, 2002. Address for reprints: Frank W. Sellke, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St, LMOB 2A, Boston, MA 02215 (E-mail: fsellke@caregroup.harvard.edu).

The first 300 words of the full text of this article appear below.

See related article on page 998.


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  		Frank W. Sellke

 
Gene therapy has been billed as a method of curing most human diseases. Despite a large amount of initial enthusiasm and a vast amount of resources spent in this area, however, except in isolated cases gene-directed treatment has yielded only modest or little success. Indeed, there have been several instances in which gene therapy has resulted in adverse events and even death. Why the limited success despite initial optimism? As with most clinical issues or problems, the answer is multifactorial. With gene therapy, it is hypothesized that by the introduction of a piece of genetic material (DNA) into the host genome, the host will be able to produce enough of a protein through translation from the resultant messenger RNA to provide beneficial results. These results can be increased blood vessel growth through angiogenesis, providing a deficient vital protein involved in immune defense, or increasing the body's ability to tolerate oxidative stress in the heart after ischemia.

First, the genetic material (DNA) needs to be incorporated into the host genome. Some investigators have attempted to inject naked DNA encoding a certain protein into the tissue at various isolated areas and have reported fairly dramatic effects. I am personally somewhat skeptical that this approach will ever have much of a role in the treatment of patients. The efficiency of transfection, or the incorporation of the DNA into the genome, is extremely low with this method, and the local delivery of the DNA to such a small locus is not likely to have a widespread effect. However, other methods of gene delivery have been more successful. Second, a promoter, either native or exogenous, needs to be present to produce, or transcribe, a significant amount of messenger RNA. Messenger RNA, as opposed to DNA, . . . [Full Text of this Article]


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Haitham J. Abunasra, Ryszard T. Smolenski, John Yap, Mary Sheppard, Timothy O'Brien, and Magdi H. Yacoub
J. Thorac. Cardiovasc. Surg. 2003 125: 998-1006. [Abstract] [Full Text] [PDF]



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