| Autor: |
Meenakshi Noll, Mark A. Kay, Stephen R. Yant, Ryan Bennett, Markus Grompe |
| Rok vydání: |
2005 |
| Předmět: |
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| Zdroj: |
Molecular Therapy. 11:S404 |
| ISSN: |
1525-0016 |
| DOI: |
10.1016/j.ymthe.2005.07.593 |
| Popis: |
The life span of patients with Fanconi Anemia (FA) is severely shortened by bone marrow failure and malignancies and currently, allogeneic bone-marrow transplantation is the only therapeutic option. Despite the successful modeling of FA viral vector gene therapy in the mouse, application of the same approach to humans is complicated by the requirement for prolonged ex vivo manipulation and the scarcity of HSCs in this disease. Here, we utilized the non-viral Sleeping Beauty (SB) transposon system to facilitate stable, gene transfer of the human FANCC cDNA without ex vivo culture. This was achieved either by electroporation of naked DNA into whole bone marrow or by direct injection into the femur cavity. Our studies demonstrate that a) hematopoietic stem cells from Fancc -/- mice can be transduced by plasmid DNA; b) stable integration of plasmid DNA into the genome of hematopoietic stem cells (HSC) is possible; c) animal model was phenotypically corrected; and d) long-term therapeutic benefit could be achieved using this method. Non-viral gene transfer may be a viable alternative for the treatment of hematopoietic diseases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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