Objective
Familial hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is predominately caused by mutations in genes that encode proteins associated with cardiac sarcomeres, the functional unit critical for basic contractile heart function. Nearly two-thirds of individuals with HCM experience mild to no symptoms, whereas the remaining one-third experience dyspnea, chest pain, or arrythmias that can progress into heart failure, causing sudden cardiac death, particularly in young competitive athletes. Current strategies to treat HCM include invasive procedures such as septal or left ventricular reduction therapies or cardiac implantation. Such methods are not curative, but rather aimed to treat symptoms and not the pathophysiological cause of the disease, thus highlighting the importance of new molecular therapies that can prevent HCM. One potential method to correct HCM mutations is through the use of antisense oligonucleotides (ASOs), short polymeric nucleic acid biomolecules, that can correct aberrant RNA splicing, a fundamental biological process for gene expression, by binding to pre-mRNA splice sites and block recognition by the spliceosome. However, delivery of ASOs to cardiac cell models, including cardiomyocytes differentiated from human induced pluripotent stem cells (iPSC-CMs), remains to be one of the biggest challenges in ASO efficacy. Herein, this project proposes to design and test the effects of chemically-modified, splice-switching antisense oligonucleotides conjugated to an antibody, an antibody-oligonucleotide conjugate (AOC), using a unique traceless linker strategy that has the potential to not only treat splicing defects in HCM, but also provide proof-of-concept of improved cell delivery of ASOs. AOCs will be tested in iPSC-CMs bearing cryptic splice mutations in MYBPC3 (myosin binding protein C), a gene whose mutations are commonly associated with HCM.
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 proteins
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences genetics RNA
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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HORIZON.4.1 - Widening participation and spreading excellence
MAIN PROGRAMME
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HORIZON.4.1.5 - Fostering brain circulation of researchers and excellence initiatives
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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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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.
(opens in new window) HORIZON-WIDERA-2022-TALENTS-04
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1649-035 LISBOA
Portugal
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.