Design, synthesis and investigation of substituted oligonucleotides for the regulation of gene expression

Project Information

Grant agreement ID: FMBI983443

Project closed

Start date 1 December 1998

End date 30 November 1999

Funded under

• Specific research and technological development programme in the field of the training and mobility of researchers, 1994-1998

Total cost No data

EU contribution No data

Coordinated by

MUSEUM NATIONAL D'HISTOIRE NATURELLE
France

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.

• 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)

• FP4-TMR - Specific research and technological development programme in the field of the training and mobility of researchers, 1994-1998

Topic(s)

• 0302 - Post-doctoral research training grants
• TC01 - Synthesis, New Molecules and Methods

Call for proposal

Data not available

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

MUSEUM NATIONAL D'HISTOIRE NATURELLE

• EU contribution: No data
• Address: 57, Rue Cuvier ; 75231 PARIS ; France
• Total cost: No data