| Gene therapy is a new kind of clinical practice which can be defined as simply as the transfer of new genetic material to the cells of an individual with resulting therapeutic benefit to the individual. The discoveries that derived from the studies on RNA and DNA tumor virus in the early 1970s led to the current gene therapy technology. Since the feasibility of genetic modification of primitive hematopoietic mouse cells was demonstrated, investigators have been developing gene therapy for the treatment of a number of congenital and acquired human diseases, β-thalassemia, one of the most common human genetic disorders, is a result of the decreased or absent synthesis of β -globin chain due to deletions or mutations in regulatory region or coding regions of β-globin gene. At the present time, therapeutic options for this disease are limited and, with the exception of allogeneic bone marrow transplantion(BMT) is only available to a minority of patients who have an HLA-matched donor, and even then the procedure is associated with significant risk of fatal complications. Gene therapy is an attractive alternative to the transplantation of allogeneic bone marrow. Theoretically, when the normal human β -globin gene is introduced into hematopoietic stem cells and the long-term regulated expression of the transduced gene in vivo is obtained, the β -thalassemic patients will be cured permanently. Presently, retroviral vectors are the most promising means for gene transfer into hematopoietic stem cells because of their high efficiency in delivery. Three requirements need to meet for successful gene therapy of β -thalassemia using retroviral vectors:(1) the stable integration of human β -globin gene into the chromosome of target cells; (2) the generation of high titer of vectors; (3) high levels of β -globin gene expression in an position-independent and erythroid-specific manner.
|
PDF Full Text Request