DESCRIPTION: (Taken from the abstract) The proposed experiments are based on the hypothesis that the ability to transduce hematopoietic stem cells (HSC) with curative or protective genes could result in a short term or permanent cure for many different diseases including AIDS. Advances in the isolation, characterization and culture of human hematopoietic CD34+ cells with extensive in vivo repopulating potential have been recently described. These developments have facilitated their evaluation as suitable targets for bone marrow transplantation and human gene therapy approaches to treat a variety of diseases. In the Progress Report of this competitive renewal, the investigator demonstrates that lentiviruses based vectors transduce human CD34+ and CD38- cells with high efficiency under conditions that maintain their in vivo repopulating potential. Furthermore, experiments show that transduced CD34+ cells can be induced to differentiate in culture resulting in sustained expression of the transgene in de-differentiated cell types, such as thymocytes. In this competitive renewal, the investigator proposes to further these observations in an in vivo human/mouse xenograft model. The following specific aims are proposed: 1) To determine the in vivo repopulating potential of lentivirus vector transduced hematopoietic stem cells, 2) To assess human T cell differentiation in NOD/SCID mice transplanted with transduced human CD34+ cells and implanted with human thymus and 3) To evaluate dominant selection for the in vivo enrichment and expansion of transduced human hematopoietic stem cells. Progress towards these goals will bring more gene therapy approaches to AIDS significantly closer to clinical implementation and further their utility as tools for discovery in basic research.