P&S Journal: Winter 1998, Vol.18, No.1
Moving Closer to Gene Therapy
Researchers at P&S have demonstrated the first high-level long-term expression of the human beta globin gene in an animal model. The study, published in the Nov. 1, 1997, issue of Blood, means that gene therapy for sickle cell disease and beta thalassemia, a related disorder, may be feasible.
In sickle cell disease, the beta globin gene produces an abnormal form of hemoglobin, the protein that transports oxygen in the blood. In beta thalassemia, the gene produces inadequate levels of hemoglobin. Theoretically, gene therapy that inserts a normal form of the beta globin gene into the bone marrow cells of patients could cure these diseases. For gene therapy to become a reality, researchers must first meet two goals: safely and efficiently transfer the normal globin, then ensure that the gene produces normal levels of its protein over long periods of time. This study is the first step toward those goals.
Senior author Dr. Arthur Bank and colleagues put a human beta globin gene into a safe retrovirus and added the virus to mice bone marrow cells. The modified cells were then transplanted into mice. The researchers were able to detect the presence of the human beta globin gene up to eight months later. The researchers also documented high levels of expression of the gene. In one mouse, 20 percent of the total beta globin it produced was from the human beta globin gene. "If we could attain that level of human beta globin gene expression in human marrow cells, it would be enough to ameliorate, if not cure, the anemia of patients with sickle cell disease and beta thalassemia," says Dr. Bank, professor of medicine and of genetics and development.
The researchers are now testing the gene transfer system in mouse models of sickle cell disease and beta thalassemia. They are also working to develop better ways to transfer retroviruses into human hematopoietic stem cells.
Other authors of the paper were Dr. Harry Raftopoulos and Maureen Ward at P&S and Dr. Philippe Leboulch, a Harvard and MIT researcher.