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Plans to Move Gene Therapy to New Plateau

By Elisheva A. Lambert

Gene therapy, one of the most recent, complex and promising medical technologies, may just have moved theory closer to practice, thanks to a trail-blazing initiative at the Harvard Medical School (HMS).

HMS recently unveiled The Harvard Gene Therapy Initiative (HGTI)--the first program of its kind.

"There has never really been a co-ordinated [gene therapy] program," said Dr. Glenn Dranoff, assistant professor of medicine.

The initiative has a tripartite goal: to guide pre-developed gene therapy approaches through clinical testing, to use current research to devise new treatment strategies and to develop a more thorough understanding of the scientific basis for genetic medicine.

Traditional treatments are designed to strengthen the body's natural defenses or to maintain health--antibiotics accomplish this by helping to fight infection. Gene therapy, however, alters the defenses themselves.

The therapy strategically splices foreign DNA--which direct the assembly of specific proteins--into the cells of certain tissues. Researchers hope that when these proteins are expressed, they will allow the body's normal metabolic and immune systems to react in lethal fashion, either killing the disease or fixing the defect in the original gene.

Right now, the process of combining foreign DNA with the DNA of vulnerable normal cells is only possible in the laboratory.

Desirable genes are transferred into tissues which have been removed from patients. The altered, hardier tissue is then reinserted into the patient. If the procedure succeeds, the patients will begin to produce the new protein as though it had always been part of their DNA.

Applications of Gene Therapy

Several applications are currently being examined for this potentially powerful technique.

Dr. David T. Scadden, associate professor of medicine at HMS, is using gene therapy to fight HIV. He is inserting a hybrid gene--part HIV-receptor and part T-cell activator--into patients' T-cells.

T-cells are normally disabled by HIV. Scadden and his team hope the genetically-altered T-cells will become HIV hunters instead of hosts, and in the future will be used to clear hidden reservoirs of HIV remaining after drug treatment.

Hersey Professor of Theory and Practice of Physic Dr. Victor J. Dzau is exploring another possible use for gene therapy.

With his colleagues, Dzau, who is the chief of medicine at Brigham and Women's Hospital, is attempting to decrease the discouraging 50 percent rate of vein collapse in patients following bypass surgery.

The collapse is frequently due to an aggressive form of arteriosclerosis precipitated by the surgery, which stimulates vein cells to divide.

Dzau's current strategy is to use gene therapy to insert a cell-division inhibitor into the vein cells. This could prevent the veins from overgrowing thereby protecting the patients.

Dranoff, is also examining possible gene therapy treatments. He is using the technique to combat cancer, by enlisting the immune system in a full-blown barrage against every malignant cell in the body.

Dranoff, whose work is currently undergoing phase one clinical trials, is optimistic about the HGTI and its benefits.

The initiative is "an attempt to provide an organized structure to have people with common interests come together," Dranoff said.

The HGTI will combine a core laboratory with an affiliated network of researchers and four small facilities in participating hospitals.

This core lab will serve as a manufacturing facility for the viral vectors necessary to transfer foreign DNA into tissue cells. The facility frees them from the need to cajole private biotech firms into manufacturing the vectors at very high cost, Dranoff said, and allows for more exploratory and small-scale testing.

"Academics do a lot of things that industry wouldn't necessarily do at the beginning," Dranoff said.

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