Abstract

A wide array of human diseases could potentially be treated by genetic manipulation of hematopoietic stem cells. However, while transfer of genetic material into murine hematopoietic progenitor cells is routinely efficiently achieved, gene transfer into stem cells of large animal models and humans has thus far proven to be difficult and inefficient.
The aim of this project is to gain insights into the biology of the hematopoietic stem cell by using in vitro and in vivo animal models of human hematopoiesis and to improve the efficiency of gene transfer/correction of this rare and elusive target cell. Human hematopoietic progenitors are obtained from cord blood or bone marrow of volunteer donors, cultured and genetically engineered in vitro, and then allowed to differentiate into mature cell lineages in vitro (CFU or LTC-IC assays) or in vivo, using mouse or sheep animal models. - SCID, Stem cells, Gene Therapy, Genetic Vectors, Immunodeficiency, Bone Marrow, Hematology, Immunology, Pediatric Research

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Intramural Research (Z01)
Project #
1Z01HG000121-02
Application #
6290331
Study Section
Special Emphasis Panel (CGTB)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
National Human Genome Research Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Yokoyama, Tadafumi; Yoshizaki, Ayumi; Simon, Karen L et al. (2015) Age-Dependent Defects of Regulatory B Cells in Wiskott-Aldrich Syndrome Gene Knockout Mice. PLoS One 10:e0139729
Uchiyama, Toru; Adriani, Marsilio; Jagadeesh, G Jayashree et al. (2012) Foamy Virus Vector-mediated Gene Correction of a Mouse Model of Wiskott-Aldrich Syndrome. Mol Ther :
Bosticardo, Marita; Ghosh, Amrita; Du, Yang et al. (2009) Self-inactivating retroviral vector-mediated gene transfer induces oncogene activation and immortalization of primary murine bone marrow cells. Mol Ther 17:1910-8
Sokolic, Robert; Kesserwan, Chimene; Candotti, Fabio (2008) Recent advances in gene therapy for severe congenital immunodeficiency diseases. Curr Opin Hematol 15:375-80
Muul, Linda Mesler; Candotti, Fabio (2007) Immune responses to gene-modified T cells. Curr Gene Ther 7:361-8
Sakamoto, Norihisa; Tsuji, Kazuhide; Muul, Linda M et al. (2007) Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans. Blood 110:501-8
Thrasher, Adrian J; Gaspar, H Bobby; Baum, Christopher et al. (2006) Gene therapy: X-SCID transgene leukaemogenicity. Nature 443:E5-6; discussion E6-7
Xu, Lai; Tsuji, Kazuhide; Mostowski, Howard et al. (2004) A convenient method for positive selection of retroviral producing cells generating vectors devoid of selectable markers. J Virol Methods 118:61-7
Bosticardo, Marita; Witte, Iren; Fieschi, Claire et al. (2004) Retroviral-mediated gene transfer restores IL-12 and IL-23 signaling pathways in T cells from IL-12 receptor beta1-deficient patients. Mol Ther 9:895-901
Bailo, Marco; Soncini, Maddalena; Vertua, Elsa et al. (2004) Engraftment potential of human amnion and chorion cells derived from term placenta. Transplantation 78:1439-48

Showing the most recent 10 out of 22 publications