ABSTRACT
Severe combined immune deficiency (SCID) is a clinical phenotype marked by the congenital absence of T- and B-lymphocyte function. The clinical syndrome of SCID is marked by acute and chronic infections due to the severe immunodeficiency. SCID is caused by a variety of mutations that interfere with the differentiation or function of T-lymphocytes or of both T- and B-lymphocytes. The optimal treatment for SCID continues to be bone marrow transplant (BMT) from a human leukocyte-antigen (HLA) matched sibling donor. Gene therapy has been considered as a potential alternative therapy to allogeneic BMT for SCID for at least a decade. Since 1986, enzyme replacement therapy for ADA-deficient SCID has been available as an alternative to haploidentical bone marrow transplantation. A primary reason that SCID has been a major focus for initial attempts at human gene therapy is that, even with the technical limitations to transducing a high percentage of target cells, a clinical benefit may be achieved.
