Objective
OBJECTIVES
* Molecular & genetic analysis of the role of the vascular endotheli al growth factor system in blood vessel formation during embryonic vascular deve lopment and pathological neovascularization.
* Viral and non-viral gene transfe r of vascular endothelial growth factor to improve ischemic heart disease.
Development of new blood vessels is essential for embryonic development and during pathological disorders such as ischemic heart and tissue disease, atherosclerosis, cancer, diabetes, wound healing and inflammation. A novel family of angiogenic growth factors, related to the vascular endothelial growth factor (VEGF) has been identified. These factors are unique and different from most other angiogenic factors by their secretion, potency and endothelial cell specific action. To date, their role in vivo during pathological vascular development is, however, largely elusive and indirectly deduced from gene expression studies. Despite its incompletely understood role in vivo, VEGF is currently being developed for (gene)therapy. Therefore, better insights in the in vivo role of VEGF and its family members is mandatory. This will allow more rational design of treatments for disorders resulting from either reduced blood vessel growth (tissue ischemia) by promoting neovascularization, or from excessive blood vessel growth (cancer, diabetic retinopathy) by preventing neovascularization.
The objectives of this proposal are to generate transgenic animal models with over- or under-expression of wild type or mutant family members of VEGF, or with a genetically defined alteration in their expression pattern (tisse-specific inactivation and conditionally induced VEGF expression). Blood vessel formation, and the impact of its abnormalities as a consequence of the genetic manipulations, during ischemic heart disease, stroke, atherosclerosis, retinopathy, wound healing and cancer will be analysed.
In addition, the proposal aims at designing and delivering (viral and non-viral) gene-therapy protocols and of reagents for the treatment of ischemic heart and tissue ischemia, and wound healing. Therefore, two innovative gene-technologies will be employed: Gene targeting via homologous or site-specific (Cre/loxP) recombination in embryonic stem cells and/or zygote injection of transgenes to generate transgenic animals. Recombinant adenoviral vectors and non-viral vectors for gene transfer of VEGF in vivo. More than half of the critical milestones, essential for the assessment of this proposal (e.g. the availability of transgenic mice with germline transmitted genetic alterations, and of recombinant adenoviral vectors) have been achieved, guaranteeing successful completion of the stated objectives.
This proposal has direct implications for exploitation of the results towards industry. Two biotechnology companies are collaborating on this project, and will form the medium to transfer and transform the insights and know-how resulting from these transgenic and gene transfer studies, into potential therapeutic drug strategies. Furthermore, the transgenic animal models will be available for the scientific (academic and industrial) community as test models for (gene)therapy. We believe that this proposal has the potential to definitively establish the role of the VEGF system in health and disease and to suggest new approaches for the development of somatic gene therapy.
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.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- medical and health sciences clinical medicine ophthalmology retinopathy
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Programme(s)
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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.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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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
3000 LOUVAIN / LEUVEN
Belgium
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.