Muscle Gene Therapy

Gene therapy researchers deliver new genes with something typically associated with illness— a virus. They take the harmless material out of the virus shell, and replace it with the gene they are interested in delivering.

"So the virus actually serves like a cargo [ship]," explains Xiao. "So when the virus contacts the cell, it will dump the gene, unload the cargo, into the cell. Then the virus will fulfill its role and disappear," while the gene goes to work.

But most of these virus cargo ships are too big to pass through blood vessels. So delivering a gene to the muscles required multiple injections directly into all the muscles researchers wanted to affect— until now.

While testing different virus shells to see which would be most effective, Xiao found that one called AAV8 was particularly good at delivering a therapeutic muscle gene to the muscle cells of a mouse, after an injection into the abdominal cavity. He was encouraged by the result, but surprised.

As time went on, the gene was expressed in virtually every muscle cell of hamsters. image: Xiao Xiao

"The entire animal now will shed green light, so the gene is basically expressed in every muscle cell," Xiao says. "We are surprised, because we did not expect such a high efficiency."

It's that kind of efficiency that frightens sporting officials wary of a future riddled with athletic "gene doping." Xiao is aware of that concern, but says that shouldn't stop him.

"We cannot be deterred just because of that concern and stop the development of gene therapy approaches for genetic disease and life threatening disease," he says.

He also points out that there's a long way to go to prove that AAV8 is safe. In fact, he found that the fluorescent gene was delivered to places one might not want it— like the liver and pancreas.

For now Xiao encourages regulations that keep gene therapy in the arena of medicine, and off the field of play. His next study will use AAV8 to try to deliver a gene that fixes damaged muscles in hamsters with a form of muscular dystrophy.

Xiao's study was published in Nature Biotechnology's advance online edition on February 27, 2005. The work was funded by the National Institutes of Health.