GENE-THERAPY IN PERIPHERAL-BLOOD LYMPHOCYTES AND BONE-MARROW FOR ADA(-) IMMUNODEFICIENT PATIENTS

Adenosine deaminase (ADA) deficiency results in severe combined immuno deficiency, the first genetic disorder treated by gene therapy. Two di fferent retroviral vectors were used to transfer ex vivo the human ADA minigene into bone marrow cells and peripheral blood lymphocytes from two patients undergoing exogenous enzyme replacement therapy. After 2 years bf treatment, long-term survival of T and B lymphocytes, marrow cells, and granulocytes expressing the transferred ADA gene was demon strated and resulted in normalization of the immune repertoire and res toration of cellular and humoral immunity. After discontinuation of tr eatment, T lymphocytes, derived from transduced peripheral blood lymph ocytes, were progressively replaced by marrow-derived T cells in both patients. These results indicate successful gene transfer into long-la sting progenitor cells, producing a functional multilineage progeny.