Objective
Cardiovascular diseases remain the primary cause of morbidity and mortality in the western countries. Pharmacological treatment improves survival and quality of life, but does not reverse disease progression. Gene therapy could fill this void, owing to its ability to treat the underlying cause. Adeno-associated viruses (AAV) emanated in the past decade as potent vectors, owing to their tropism for specific tissues, their low immunogenicity, their lack of pathogenicity and their ability to sustain long-term expression. As a testament to their potential, the European Commission approved the first gene therapy (Glybera) and several cardiac gene therapy clinical trials, one phase IIb, are underway using AAVs for gene targeting. Despite their growing success, a major impediment is the presence of pre-existing antibodies in patient serum, which excludes almost 50% of the population from clinical trials. The currently prominent approach, generation of novel serotypes from the known cardiotropic ones (AAV6 and 9) by random mutagenesis, alters favorable serotype attributes and most importantly tropism.
Our goal is to generate novel serotypes based on AAV6 and 9, using a directed mutagenesis approach, against only the amino acids involved in neutralization but not receptor binding and therefore tropism. The mutant AAVs will be tested in vitro and in vivo for neutralization, transduction efficiency and cardiac tropism. Alternatively, a semi-random mutagenesis library approach focusing on 3-5 key amino acids will be pursued.
Overall, the proposed study, using standard molecular biology techniques, will produce an immunogenic map of the cardiotropic AAVs, generate a panel of novel AAVs that evade humoral immunity but retain tropism, and therefore unequivocally provide with most needed vectors for human clinical trials and the opportunity for personalized medicine. Finally, this strategy will provide a proof of principle for other serotypes and diseases.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences medical biotechnology genetic engineering gene therapy
- medical and health sciences clinical medicine cardiology cardiovascular diseases
- medical and health sciences health sciences personalized medicine
- natural sciences chemical sciences organic chemistry amines
- natural sciences biological sciences molecular biology
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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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IIF
See other projects for this call
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
69120 HEIDELBERG
Germany
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.