NEW YORK -- In an astonishing result, scientists altered a gene in rats' livers by injecting a "repairman" molecule into the animals' bloodstreams. The technique might lead to a cure someday for hemophilia and some other inherited diseases in people.
The startling thing was how well it worked. The treatment produced a specific change in about 40 percent of the rat liver's supply of the targeted gene. Other techniques have achieved rates more like one in a million, even when tried on cells in laboratory dishes rather than in an animal.
A 40 percent success rate could cure many genetic diseases. But gene therapy experts cautioned that it's not clear whether this technique would apply to a range of disorders. They also noted that many scientists have not been able to make it work.
If the technique works in people, it might cure an inherited form of high cholesterol that affects about one in 500 people and gives them heart attacks around age 40. Other liver targets, apart from hemophilia, are mostly rare diseases. But with modification, the technique might also treat some other genetic diseases outside the liver.
"We were surprised ourselves by how efficient it was," said Dr. Clifford J. Steer of the University of Minnesota, who reports the work with colleagues in the March issue of the journal Nature Medicine.
Most gene therapy experiments haven't tried to fix a bad gene. Instead, they've supplied cells with working copies of a gene to step in for the defective version. Fixing the bad gene would be better, but the low efficiency in past experiments has been discouraging.
To show that the technique works, Steer's rat study used the technique to alter a healthy gene rather than correcting a bad one. But researchers now plan a study in dogs to fix a flawed gene that causes hemophilia, he said.
The repairman molecule had two main parts. One was a tag to make liver cells grab the repairman when it passed by in the blood. The other part contained a mix of DNA and its chemical cousin RNA, designed to seek out a particular piece of the gene for a clotting substance called factor IX.
Once the repairman showed up there, the cells replaced that piece of gene with the substitute brought by the repairman. How that works is still a bit of a mystery, but it probably involves the body's natural mechanism for repairing genetic flaws, Steer said.
Dr. James M. Wilson, a gene therapy expert at the University of Pennsylvania, said a big question is how well the technique would work against a variety of genetic flaws. "If it's not generic, and it only functions in a subset of patients with rare diseases, it's not going to have the kind of impact that gene therapy needs to have," he said.
In a Nature Medicine commentary, gene researcher Michael Strauss of Humboldt University in Berlin said most researchers who've tried the technique have not been able to make it work.
Steer's result is "both very inspiring and very controversial," he wrote.
Steer is optimistic. "We will make it work in people," he said. "This is a remarkable technology."
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