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Researchers Develop New Therapy to Correct Defective Gene

Scientists say they've developed a highly effective therapy to correct a defect in the gene that's responsible for the so-called "bubble-boy" disease. They say it's likely the technique would be effective in treating a host of other disorders, including AIDS.

The promise of curing disease through gene therapy has remained elusive because researchers have yet to find a way to replace healthy genes with diseased ones.

That was demonstrated in the case of three little boys in France who suffered from SCID or bubble-boy disease, a rare disorder in which patients suffer from a severely impaired immune system that usually results in death from infection. Researchers tried to replace the faulty gene responsible for SCID by attaching it to a virus. But the virus triggered a negative immune response, and the boys developed leukemia.

Since then, scientists have been working to develop an entirely different genetic delivery mechanism using so-called zinc fingers, which occur naturally inside the nucleus of each cell and bind to DNA, turning genes on and off. It's this genetic expression that determines whether someone develops a particular disease. Experts say zinc fingers are easily engineered to carry correct genetic information inside the cell.

In a study reported this week in Nature, scientists at Sangamo BioSciences in California report, using altered zinc fingers to permanently correct 20 percent of genes they studied that are responsible for SCID. While that doesn't sound like a huge percentage, it's very encouraging by scientific standards.

Michael Holmes, who headed the study, says "what makes this an improvement is that we're actually correcting the gene that's mutated. We're not adding extra or foreign sequence to the cell. What our technology does is we go in and actually repair the gene that's mutated."

Edward Landphair is Sangamo's president. "The technology is very powerful and very general and allows us to target any gene that we want in the genome and the approach that we're taking is targeting genes where there's a mutation, or mistake in that gene, that leads to a specific disease," he says.

But scientists say zinc fingers are designed to treat diseases that are caused by a single, defective gene, such as sickle cell anemia.

Mr. Landphair says researchers are moving ahead with studies that use zinc fingers as a treatment for AIDS. "Specifically, going after a gene that allows the HIV virus to get into cells of the immune system. And by blocking or disrupting the gene that makes that receptor, we hope to protect cells of the immune system from HIV infection. And that's a program we're working to get into the clinic in the next 12 to 18 months," he says.

Mr. Landphair says other studies are also looking at the use of zinc finger gene therapy in the treatment of some cardiovascular diseases and diabetic neuropathy.