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Biocompatible non-viral polymeric gene delivery systems for the ex vivo treatment of ocular and cardiovascular diseases with high unmet medical need

Biocompatible non-viral polymeric gene delivery systems for the ex vivo treatment of ocular and cardiovascular diseases with high unmet medical need

Objective

The objective of this proposal is to develop a non-viral ex vivo gene therapy that will be applied for both ocular and cardiovascular diseases with high-unmet medical need. The research of the project focuses on improving polymeric DNA-delivery by combining polyplexes with cell penetrating peptides (CPP). To circumvent the toxic and immunogenic problems related to viral vectors, the gene vectors developed in this project will be a non-toxic and non-immunogenic, biodegradable polymeric carrier based on multifunctional poly-alpha-amino acids. The potential of the CPP-containing polyplexes regarding their transfection efficiency and the absence of any toxic or immunogenic side effects will be evaluated using two gene transfer approaches. In a first approach, cells will be transfected with polyplexes (i.e. polymer-DNA complexes) and then seeded on an electrospun polymer membrane prior to implantation.

Alternatively, the polymer membrane will be surface coated with polyplexes prior to cell seeding and implantation. In order to enhance the internalisation efficiency, the polyplexes will be functionalised using Penetratin-like CPP. In order to improve the membrane-cell interaction and to enhance the cell proliferation and differentiation, the polymer membrane will be functionalised with cell interacting peptides (CIP).

To reach the final project goal, different work packages will be implemented:
(1) selection of CIP and CPP,
(2) development of CPP-containing polymers,
(3) development of CIP-containing polymer membranes by electrospinning,
(4) preparation of plasmids and CPP-containing polyplexes,
(5) characterisation of polyplex-cell and polymer membrane-cell interactions,
(6) study on immunological properties of polyplexes and polymer membranes and
(7) polymer membrane implantation in test animals.

Work package 8 will be devoted to the project management.

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Coordinator

GHENT UNIVERSITY

Address

Sint Pietersnieuwsstraat 25
Ghent

Belgium

Administrative Contact

Peter DUBRUEL (Prof.)

Participants (8)

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HELSINGIN YLIOPISTO

Finland

INSTITUTE OF MICROBIOLOGY ACADEMY OF SCIENCES OF THE CZECH REPUBLIC

Czechia

EBERHARD-KARLS-UNIVERSITY TUEBINGEN

Germany

UNIVERSITY OF KUOPIO

Finland

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

France

ARK THERAPEUTICS LTD

United Kingdom

ECOLE NORMALE SUPÉRIEURE /CNRS UMR 8542

France

FRAUNHOFER-GESELLSCHAFT ZUR FÖRDERUNG DER ANGEWANDTEN FORSCHUNG E.V

Germany

Project information

Grant agreement ID: 19114

  • Start date

    1 June 2006

  • End date

    30 November 2009

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 2 847 586

  • EU contribution

    € 2 132 607

Coordinated by:

GHENT UNIVERSITY

Belgium