Beta-thalassemia is a genetic blood disease in which the red blood cells have an abnormal form of the oxygen-carrying molecule called hemoglobin (Hb). Normal Hb is made up of two alpha-globin proteins and two beta-globin proteins. The defective red blood cells in beta-thalassemia arise from hematopoietic stem cells (HSCs) in which both genes for beta-globin are either missing or mutated. In the absence of beta-globin, the other building block of Hb, alpha-globin, accumulates and eventually destroys the red blood cell. HSCs are parent cells in the bone marrow that give rise to blood cells.
The St. Jude team successfully treated beta-thalassemia in mice by using a newly developed vector--or biological ferry composed of DNA housed within a harmless virus--to shuttle a therapeutic gene into the defective HSCs. The gene allowed red cells that were derived from the HSCs to make gamma-globin, a protein that acted as a substitute for beta-globin. The resulting Hb molecule, composed of alpha- and gamma-globin, is called fetal Hb (HbF) because it normally occurs only during the fetal stage of development. The use of HbF prevents the need to introduce normal beta-globin into the body in someone who has never had it before. It is possible that the sudden introduction of beta-globin could trigger an immune response against this protein.
The vector, which used a virus called lentivirus to carry the gamma-globin gene, also carried a special set of additional pieces of DNA called regulatory elements. These elements were part of a section of the normal chromosome containing t
Contact: Bonnie Cameron
St. Jude Children's Research Hospital