Glowing evidence of gene-altered arteries.

One of summer's delights is the pulsing glow of hundreds of fireflies dotting the dusky sky. New research suggests that this same power source can help light the way to a gene therapy for coronary artery disease.

A 1989 report of the first successful transfer of a bacterial gene into the leg arteries of live animals (SN: 6/17/89, p.373) took molecular biologists one step closer to the prospect of a gene therapy for humans who suffer from clogged arteries. Researchers have now added a luminous twist to such experiments, this time inserting dog arteries with the gene coding for luciferase -- the enzyme that gives the firefly its "fire."

In one experiment, Judith L. Swain and her colleagues at Duke University Medical Center in Durham, N.C., anesthetized seven dogs and surgically exposed the femoral arteries of the legs. They then inserted catheters and flushed the arteries with a solution containing luciferase genes. The enzyme's glow, they reasoned, would signify gene activation. After three days, they removed the tissue and exposed it to a light-measuring device.

In six of the animals, the glow-meter readings indicated that the altered femoral tissue contained 1 to 77 picograms of luciferase, averaging about 20 picograms. This showed that the gene had traveled through the cell membrane and "turned on," directing the canine cell to secrete the firefly enzyme, Swain's group reports in the June CIRCULATION. In a separate experiment, the team transferred the luciferase gene into the coronary arteries of two dogs, later detecting 28 and 32 picograms of the enzyme.

While no one proposes injecting firefly genes into people, the study does brighten hopes that scientists may someday inject human coronary arteries with genes that code for powerful clot-dissolving proteins such as tissue plasminogen activator (TPA), Swain says. The inserted genes might turn artery cells into miniature TPA factories that churn out enough of the drug to prevent the blood clots that can trigger a heart attack, she adds.

People undergoing angioplasty, in which doctors use a tiny balloon to open clogged arteries, might be prime candidates for such gene therapy, Swain suggests. Although physicians currently give angioplasty patients intravenous injections of TPA, this doesn't always prevent the arteries from later reclogging or developing clots. Swain cautions, however, that a gene therapy to keep human arteries open will take many more years to develop.