Objective
The objectives of this project is the design of non-viral gene transfer vectors that are applicable for ex vivo and in vivo gene therapy.
For many years, much effort has been devoted towards development of appropriate carriers for delivery of drugs and macromolecules, including nucleic acids (e.g. plasmids) into cells. Progress in somatic gene therapy is strongly influenced by the development of systems for efficient and safe delivery of genetic information into target cells. While several efficient vector systems (viral and non-viral) are available for ex vivo gene therapy, in vivo gene therapy is strongly hampered by the lack of efficient and target-specific vectors. Non-viral gene transfer systems, although not yet reaching the efficiencies of viral vectors, are attractive because they are very flexible regarding the size of DNA to be transported; the entire diversity of chemical reactions and physical interactions under non-physiological conditions may be utilized for their synthesis (in contrast to biological vectors); safety testing is less laborious than testing of biological systems, and they can be produced at large scale with low costs. The application of synthetic vectors to transfect cells is hampered by their relative low efficiency compared to viruses, low reproducibility, cell toxicity, and cell selectivity. Thus, there is an urgent need in fundamental as well as technological knowledge on the following points which are particularly relevant for applications in gene therapy: (i) mechanism of interaction between amphiphiles and cells, (ii) specific targeting of nucleic acid/amphiphile complex, (iii) transfection efficiency of gene delivery, and finally (iv) applications to in vivo models.
To reach this objective the project will focus on the following issues: 1 - Construction of new non-viral carriers, capable of introducing nucleic acid (plasmids, antisense oligonucleotides, genes) into target cells, incorporating some characteristic viral entry functions. These vectors will be defined by:
a). A great capacity of nucleic acid loading,
b) . A capability to deliver nucleic acids into cytoplasm, as viruses do, c) . A great specificity for target cells.
2 - Studies of the interactions of the different vectors with cells in order to increase our knowledge of the basic mechanism of nucleic acid delivery (interaction process, nucleic acid processing into cells, cell defense...) and, to improve the characteristics of the vectors (reproducibility, toxicity, stability, efficacy...)
3 - Efficiency measurements of the vectors in-vitro, according to two different processes, in order to select the best in vivo systems:
a) . Expression of a reporter gene in recipient cells,
b) . Expression of functional genes (e.g. apoptic genes),
4 - Applications of selected vectors to the treatment of in vivo models (human EGP 2 tumor in transgenic rats and murine melanomas M3 and B16 in immunocompetent syngeneic animals) or treatment of malignant hematopoietic cells ex vivo.
The carrying out of the project will be made possible thanks to a multi-disciplinary approach combining complementary disciplines and techniques (organic chemistry, cell biology, biochemistry, biophysics, molecular biology) which might impinge on future medical, veterinary and agricultural applications. This will be facilitated by the participation of an industrial partner which has already a strong experience in gene delivery and its aonlication
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- medical and health sciences medical biotechnology genetic engineering gene therapy
- natural sciences chemical sciences organic chemistry
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine oncology skin cancer melanoma
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
34095 MONTPELLIER
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.