Objective
The regulatory functions of RNAs rely on their propensity to adopt defined secondary structures. G-rich nucleic acid sequences have a propensity to form highly stable four-stranded structures (termed quadruplexes) in the presence of physiological monovalent cations. Using an approach that consists in targeting simultaneously the quadruplex structure itself but also the two single-stranded RNA flanking regions in a sequence-specific manner, we demonstrate that RNA quadruplexes represent a valid therapeutic target for chemical intervention to modulate the translation of specific genes (notably N-Ras, Aurora kinases A and C) both in vitro and in vivo. Peptide nucleic acids (PNAs) are used as antisense oligonucleotide analogues to direct a quadruplex-stabilising platform to the only gene of interest, thus making this class of compounds capable of discriminating between an RNA quadruplex and other nucleic acid secondary structures, including other RNA quadruplexes. This novel approach for specifically silencing genes is likely to have great therapeutic potential. Once validated in vitro, this strategy will be applied in vivo, using for the first time microbubbles to facilitate the delivery of neutral oligonucleotide analogues (i.e. PNAs) in cellulo. Co-injection of microbubbles and antisense oligonucleotides, combined with localised ultrasound treatment has been successfully applied for gene delivery to specific organs. Herein, transfection of the PNA-based RNA quadruplex ligands will be carried out using microbubbles with variable shell compositions and different transfection methods (co-injection, encapsidation, covalent attachment) will also be considered. Transfection efficiency will be quantitatively evaluated by fluorescence confocal microscopy and correlated with the changes in levels of expression of specific genes.
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
- natural sciences physical sciences optics microscopy confocal microscopy
- natural sciences biological sciences genetics RNA
- natural sciences physical sciences acoustics ultrasound
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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-2011-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
SW7 2AZ London
United Kingdom
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.