Gene therapy promises solution for sickle cell disease
Researchers from Columbia University College of Physicians & Surgeons have demonstrated for the first time the transmission and subsequent expression of the human betaglobin gene over a prolonged period in a mouse experiment. The knowledge gained could lead to the development of gene therapy for sickle cell anemia and beta-thalassemia, a related disorder. Arthur Bank, M. D., a Columbia University professor and director of the Department of Hematology, and his colleagues inserted a human betaglobin gene into a harmless retrovirus and introduced the virus into mouse bone marrow cells in vivo. The modified cells were then transplanted into live mice. The human betaglobin gene could still be detected up to eight months later. The researchers also found a very high level of gene expression: in one mouse, 20 percent of all betaglobin produced came from the inserted human gene.
"If we could achieve this level of gene expression in a patient with sickle cell disease or beta-thalassemia bone marrow cells, it would be sufficient to ameliorate, if not cure, the diseases," says Bank.
In sickle cell disease, the betaglobin gene produces an abnormal form of hemoglobin, the oxygen-carrying molecule in the blood. The damage causes the red blood cells to deform. The then crescent-shaped blood cells get caught in the small blood vessels. This impairs the circulatory system and damages various organs. In addition, sickle cells have a shorter lifespan. This leads to severe anemia. In beta thalassemia, the gene produces insufficient amounts of hemoglobin. Theoretically, by inserting a normal form of the betaglobin gene into the patient's bone marrow cells, gene therapy can cure these diseases.
"For more than 10 years, researchers have been searching for a reliable delivery system for delivery of the human betaglobin gene and subsequent expression over extended periods of time. This is the first time that researchers have safely and efficiently transferred the normal globin gene and verified that this gene produces normal levels of its protein over long periods of time,” says Dr. Bank.
While the studies described so far were carried out on he althy mice, the scientists are now investigating effective gene transfer systems in experiments on mice suffering from sickle cell anemia and beta-thalassemia. In addition, they are working to develop better methods of transferring the retroviruses into human hematopoietic stem cells.
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