ADA-transduced hematopoietic stem cells for severe combined immunodeficiency disease

These studies evaluate gene therapy treatment in which the adenosine deaminase (ADA) gene is retrovirally delivered into hematopoietic stem cells and transplanted in patients with severe combined immunodeficiency disease (SCID) due to a mutant ADA gene. The SCID patients were treated with nonmyeloablative chemotherapy, followed by an infusion of autologous hematopoietic stem cells that had been transduced with a retroviral vector bearing the ADA gene. In the first trial, the cells were transduced with 2 different vectors, in order to compare their efficiency in vitro. There was no consistent advantage to transduction by either vector. In the 2nd trial, the cells were transduced with the MND-ADA retroviral vector. Substantial levels of gene-corrected T-lymphocytes expressing ADA enzyme activity and supporting immune reconstitution were recorded.