Gene Therapy In A Liquid May Lead To Quicker, Easier Methods For Treating Disease

Neuroscientist Matthew During, M.D., professor of neurosurgery and director of the Central Nervous System Gene Therapy Center at Thomas Jefferson University in Philadelphia, and his colleagues put a gene for lactose intolerance inside a virus, and then into a liquid solution. When they gave the solution to laboratory rats, the gene began working in about 20 percent of the rats' proximal intestinal cells--enough, he says, to correct the experimentally induced lactose intolerance in the animals. The effect lasted four months, the length of the experiment.

He and his co-workers report their findings in the October issue of Nature Medicine.

Dr. During and his colleagues inserted a beta-galactosidase gene--which encodes for an enzyme that breaks down lactose--into an adeno-associated virus vector. They then gave this orally through a special tube to lactose-intolerant rats. The gene incorporated into the cells lining the rats' gastrointestinal tract, allowing them to break down lactose.

"We showed several important things," he says. "We could deliver a gene noninvasively, we could achieve long-term gene expression through a simple oral route, and there was enough gene expression to treat a disease such as lactose intolerance."

The work has potential applications for treating other diseases such as diabetes, he notes, "for which you want to deliver a protein into the circulation."

The researchers' goal wasn't necessarily to find a cure for lactose intolerance--rather, they used the disorder as a model. "We used lactose intolerance to help us prove a principle--to show that an oral delivery system would work," he says.

Gene therapy, he says, has to date usually been attempted to treat rare genetic diseases, AIDS and cancer. "The idea is to eventually move it into standard medical practice."

Dr. During's group engineered a virus--adeno-associated virus--to which virtually everyone has been exposed, rendering the virus harmless. The virus is hearty and can survive the acidic environment of the stomach. "We decided to go after the world's most common genetic disease--lactose intolerance."

Lactose intolerance is a common genetic disorder that affects about half of the world's population. It results from reduced activity of an enzyme, lactase, and is characterized by an inability to metabolize lactose.

The work was supported in part by the Juvenile Diabetes Foundation International.