A clinical trial of retroviral-mediated transfer of a rev-responsive element decoy gene into CD34(+) cells from the bone marrow of human immunodeficiency virus-1-infected children

Genetic modification of hematopoietic stem cells with genes that inhibit re plication of human immunodeficiency virus-1 (HIV-1) could lead to developme nt of T lymphocytes and monocytic cells resistant to HIV-1 infection after transplantation. We performed a clinical trial to evaluate the safety and f easibility of this procedure, using bone marrow from four HIV-1-infected pe diatric subjects (ages 8 to 17 years). We obtained bone marrow, isolated CD 34(+) cells, performed in vitro transduction with a retroviral vector carry ing a rev-responsive element (RRE) decoy gene, and reinfused the cells into these subjects with no evidence of adverse effects. The levels of gene-con taining leukocytes in peripheral blood samples in the 1 year after gene tra nsfer/cell infusion have been extremely low. These observations support the potential of performing gene therapy for HIV-1 using hematopoietic cells, but emphasize the need for improved gene transfer techniques. (C) 1999 by T he American Society of Hematology.