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Combined isolation and stable non-viral transfection of hematopoietic cells- a novel platform technology for ex vivo hematopoietic stem cell gene therapy

Objective

The feasibility of ex vivo gene therapy in humans has been demonstrated with retrovirally ransduced hematopoietic stem cells. At the same time, risks associated with the use of retroviral vectors became apparent. We will establish and validate a novel combination technology for hematopoietic cell isolation and non-viral transfection leading to site-specific genomic integration of transfected nucleic acids. This novel technology will be validated by expert groups in hematopoietic stem cell gene therapy and related basic and clinical research. The technology is going to be exploited and disseminated by the company partners Miltenyi Biotech, OZ Biosciences, and Poetic Genetics.

A platform technology for non-viral 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 (CliniMACS) with magnetically enhanced transfection (Magnetofection). Cel l 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 A AV-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 based on its competitive advantage.

Call for proposal

FP6-2004-LIFESCIHEALTH-5
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Coordinator

KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITÄT MÜNCHEN
Address
Ismaninger Str. 22
Munich
Germany

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Participants (10)

COMENIUS UNIVERSITY
Slovakia
Address
Mlynska Dolna F1
Bratislava

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ERASMUS UNIVERSITY MEDICAL CENTER
Netherlands
Address
Dr Molewaterplein 50
Rotterdam

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Links
FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR
Italy
Address
Via Olgettina 60
Milano

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FRAUNHOFER GESELLSCHAFT ZUR FÖRDERUNG DER ANGEWANDTEN FORSCHUNG E.V.
Germany
Address
Hansastrasse 27c
Munich

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LUDWIG-MAXIMILIANS-UNIVERSITÄT
Germany
Address
Geschwister-scholl-platz 1
Munich

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M. SKLODOWSKA-CURIE MEMORIAL CANCER CENTER AND INSTITUTE OF ONCOLOGY
Poland
Address
Ul. W.k. Roentgena 5
Warsaw

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MILTENYI BIOTEC GMBH
Germany
Address
Friedrich-ebert-str. 68
Bergisch Gladbach

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OZ BIOSCIENCES
France
Address
Parc Scientifique De Luminy - Bat Inmed
Marseille

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RESEARCH INSTITUTE OF MOLECULAR PATHOLOGY
Austria
Address
Dr.-bohr-gasse 7
Vienna

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WEIZMANN INSTITUTE OF SCIENCE
Israel
Address
Weizmann Institute
Rehovot

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