Objective
Research objectives and content
Many human diseases arise from the dysfunction of genes. Oligonucleotides, which can form complexes with RNA or DNA by complementary base pairing, represent a new class of potential therapeutic agents for such diseases, acting directly on the nucleic acids. However, problems as the low stability of oligonucleotides in biological media, the poor penetration of oligonucleotides into cells and the reversibility of complex formation disturb the practical applications of oligonucleotides. Chemical modification of oligonucleotides, which will be the main objective of this project, could, at least partially, contribute to the resolution of these problems.The objectives of the research work will be: a)The attachment of a minor-groove-binding ligand to an oligonucleotide-intercalator conjugate (structure A), a novel and improved strategy for increasing the stability of oligonucleotide-DNA complexes.Oligonucleotide - L - intercalator - minor groove ligand (major-groove ligand)b)The employment of particular peptides as minor-groove ligands, which could exhibit several additional beneficial functions, such as a more effective internalization of the oligonucleotide or an extended range of recognition sequences. c)Synthesis of oligonucleotide-intercalator conjugates and testing for their ability to recruit topoisomerases (and, | possibly, other DNA-cleaving enzymes) for site-directed DNA damage.d)Elaboration of a reliable and versatile scheme for the modification of non-protected oligonucleotides which could be applied to a large variety of different ligands.e)The synthesized products will be tested in the appropriate system for their anti-sense or anti-gene effects.
Links with industry / industrial relevance (22):
Prof Claude Helene, the supervisor is a scientific director of Rhone Poulenc Rorer.Contracts with non-industrial and state research organizations:ANRS (Agence Nationale de la Recherche sur le SIDA), ARC (Association de la Recherche sur Cancer), League contre cancer. The laboratory of Biophysics includes two Units of state research organisations: U-201 INSERM (Institut National de la Sante et de la Recherche Medicale) and URA-48 I CNRS (Centre National de la Recherche Scientifique).
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 biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biophysics
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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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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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
75231 PARIS
France
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