Retroviral marking of canine bone marrow: long-term, high-level expression of human interleukin-2 receptor common gamma chain in canine lymphocytes
| Autor: | T, Whitwam, M E, Haskins, P S, Henthorn, J N, Kraszewski, S E, Kleiman, N E, Seidel, D M, Bodine, J M, Puck |
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| Rok vydání: | 1998 |
| Předmět: |
Genetic Markers
Immunosuppression Therapy Stem Cell Factor X Chromosome Gene Transfer Techniques Gene Expression Receptors Interleukin-2 Genetic Therapy Dogs Retroviridae Bone Marrow Granulocyte Colony-Stimulating Factor Animals Humans Severe Combined Immunodeficiency Lymphocytes Bone Marrow Transplantation |
| Zdroj: | Blood. 92(5) |
| ISSN: | 0006-4971 |
| Popis: | Optimization of retroviral gene transfer into hematopoietic cells of the dog will facilitate gene therapy of canine X-linked severe combined immunodeficiency (XSCID) and in turn advance similar efforts to treat human XSCID. Both canine and human XSCID are caused by defects in the common gamma chain, gammac, of receptors for interleukin-2 and other cytokines. In this study, normal dogs were given retrovirally transduced bone marrow cells with and without preharvest mobilization by the canine growth factors granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF). Harvey sarcoma virus and Moloney murine leukemia virus constructs were used, both containing cDNA encoding human gammac. The Harvey-based vector transduced into cytokine-primed marrow yielded persistent detectable provirus in bone marrow and blood and expression of human gammac on peripheral lymphocytes. In three dogs, human gammac expression disappeared after 19 to 34 weeks but reappeared and was sustained, in one dog beyond 16 months posttransplantation, upon immunosuppression with cyclosporin A and prednisone, with up to 25% of lymphocytes expressing human gammac. The long-term expression of human gammac in a high proportion of normal canine lymphocytes predicts that retrovirus-mediated gene correction of hematopoietic cells may prove to be of clinical benefit in humans affected with this XSCID. This is a US government work. There are no restrictions on its use. |
| Databáze: | OpenAIRE |
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