For the first time scientists have corrected sickle cell disease in mice using gene therapy, according to a study supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health and published in the December 14 issue of Science.
"Scientists have been working to accomplish this since the creation of an animal model for sickle cell disease several years ago. Although much more research is needed before human application, this is a significant achievement that brings us closer to human gene therapy for what is a very serious genetic blood disorder," said NHLBI Director Claude Lenfant, M.D.
Sickle cell disease affects about 1 in 500 African Americans and 1 in 1,000 Hispanic Americans. The disease is caused by a mutation in one of the two genes that determines the structure of hemoglobin, a critical molecule found in red blood cells. Hemoglobin transports oxygen from the lungs to other parts of the body. In patients with sickle cell disease, abnormal hemoglobin molecules stick to one another and form long, rod-like structures. These structures cause the red blood cells to become stiff assuming a sickle shape. The sickled red cells pile up, causing blockages and damaging vital organs and tissue. In the study led by scientists at Harvard Medical School and the Massachusetts Institute of Technology, mice were bioengineered to contain a human gene that produces defective hemoglobin, causing sickle cell disease. The defect is an amino acid substitution on the so-called "beta" chain of amino acids that makes up part of the hemoglobin molecule. Since no single mouse model perfectly mimics human sickle cell disease, the scientists performed the experiment using two different mouse models. One mouse model contained only defective human hemoglobin and the other model contained a mixture of defective human hemoglobin and normal mouse hemoglobin.
Bone marrow containing the defective human beta-hemoglobin gene was
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NIH/National Heart, Lung, and Blood Institute