An important first step toward curing sickle-cell anemia has been reported by scientists who managed to swap a good gene for a bad one in cells growing in tissue culture.
The results do not yet offer a cure for the inherited blood ailment, but they do suggest it's possible to replace a mutated gene that ruins red blood cells with a healthy gene that corrects the defect. The inserted gene acted properly, making normal beta-globin, a part of hemoglobin.
Cures for such diseases may come when scientists learn to reliably swap good genes for bad in a patient's own tissues, such as bone marrow cells, then reimplant the corrected cells into the body. Cells corrected of the sickling defect would repopulate the bone marrow and produce normal hemoglobin.
"This is kind of a first step along the pathway" to gene therapy forsickle-cell anemia, said geneticist Edward G. Shesely at the University of North Carolina. "We had to show we could correct the defect by gene-targeting, and we've done that."
What must still be shown, he said yesterday, is that such genes can also be exchanged in human bone marrow cells, which may be more difficult. The recent work was done in hybrid mouse-human cells, which may not be representative of natural cells.
The new gene-swapping work is based on techniques developed independently by biologists Oliver Smithies at the University of North Carolina and Mario Capecchi at the University of Utah. The new sickle-cell work was done in Smithies' laboratory.
In a report in the Proceedings of the National Academy of Sciences, Shesely, Smithies and four colleagues report that the inserted gene knocked out the defective gene and also acted correctly, producing normal beta-globin. The beta-globin is part of the oxygen-carrying hemoglobin molecule in red blood cells.
The mutation that causes the disease is seen almost exclusively in black people. According to Dick Campbell, executive director of the Sickle Cell Disease Foundation of Greater New York, about one in every 400 blacks in the United States has the disease, while about one in every 10 is a carrier of the sickle-cell gene. A person must inherit a copy from each parent to get the severe form of the disease.
Sickle-cell anemia is caused by a mutated gene that makes an abnormal form of hemoglobin. It causes red blood cells to assume a crescent shape, so they tend to stick and clog small blood vessels, the capillaries.