The central theme of this Program is improving gene transfer and gene correction in human hematopoietic stem and progenitor cells to provide more effective and safe therapies for blood cell disorders. While the concept of gene therapy using HSC to provide improved methods to treat congenital disorders has been under study for at least two decades, there have been only a small number of successful clinical applications. The techniques currently in use for gene transfer and expression in HSC are sub-optimal in most cases to yield clinical benefits. The goals of this Program are to investigate the mechanisms limiting successful clinical applications of gene transfer and to develop improved techniques which will broaden the range of diseases which may be treated effectively and safely. These advances can only be realized by combining each of these individual projects into a unified Program. This Program has three projects: 1. Selective Expansion of Hematopoietic Stem Cells and Lymphoid Progenitors, 2. Genome Modification in Human Hematopoietic Stem cells, and 3. Gene Therapy for ADA-deficient SCID. Four Cores (Administrative, Cell Isolation and Analysis, Vectors and Animals) will support the projects with integrated services for optimal quality and efficiency. The Project and Core leaders have complementary expertise in the relevant areas of experimental hematology, gene therapy, immunology, and signal transduction and have a long-standing record of interactive collaborations.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL073104-09
Application #
8304127
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Qasba, Pankaj
Project Start
2003-04-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
9
Fiscal Year
2012
Total Cost
$1,863,676
Indirect Cost
$653,497
Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Urbinati, Fabrizia; Hargrove, Phillip W; Geiger, Sabine et al. (2015) Potentially therapeutic levels of anti-sickling globin gene expression following lentivirus-mediated gene transfer in sickle cell disease bone marrow CD34+ cells. Exp Hematol 43:346-51
Berent-Maoz, Beata; Montecino-Rodriguez, Encarnacion; Fice, Michael et al. (2015) The expansion of thymopoiesis in neonatal mice is dependent on expression of high mobility group a 2 protein (Hmga2). PLoS One 10:e0125414
Prashad, Sacha Leandra; Calvanese, Vincenzo; Yao, Catherine Yao et al. (2015) GPI-80 defines self-renewal ability in hematopoietic stem cells during human development. Cell Stem Cell 16:80-7

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