The feasibility of ex vivo gene therapy in humans has been demonstrated with retrovirally transduced hematopoietic stem cells. At the same time, risks associated with the use of retroviral vectors became apparent. The Magselectofection team will establish and validate a novel combination technology for hematopoietic cell isolation and nonviral transfection leading to site-specific genomic integration of transfected nucleic acids. This novel technology will be validated by Magselectofection experts in hematopoietic stem cell gene therapy and related basic and clinical research. |  A platform technology for nonviral transfection of hematopoietic cells in general and hemaptopoietic stem cells in particular, with optional stable genetic modification, will be established by integrating a clinically approved magnetic cell separation technique with magnetically enhanced transfection. Cell nucleus-targeting vectors will be applied. For selected indications, the technology will be practiced with plasmid constructs that provide site-specific genomic integration, either the phage phiC31 integrase system or, alternatively, a drug-inducible AAV-derived replicase/integrase system.
| Technology validation includes the analysis of genomic integration sites, transcriptom profiling, characterization of stable and inducible trans-gene expression and evaluation of engraftment and persistence in transgenic animal models using molecular biological tools and magnetic resonance imaging. The therapeutic potential will be examined in a SCID-X mouse model in direct comparison with established retroviral technology. Magselectofection is expected to circumvent problems associated with viral vectors, contribute to health care progress and foster the competitiveness of Europe’s biotechnology industry. |
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