Compositions for transfection of oligonucleotides active for...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/88 (2006.01) A61K 31/7105 (2006.01) A61K 31/713 (2006.01) A61K 47/24 (2006.01) A61K 47/28 (2006.01) A61K 48/00 (2006.01) A61P 31/12 (2006.01) A61P 33/00 (2006.01) A61P 35/00 (2006.01) C12N 15/87 (2006.01) C07D 233/56 (2006.01) C07D 235/06 (2006.01) C07D 277/22 (2006.01) C12N 15/11 (2006.01)

Patent

CA 2648520

The invention relates to compositions of transfection comprising an oligonucleotide and an amphiphilic cationic molecule of formula (I) wherein, - X is N-R1, S or O, R1 being a C1-C4 alkyl radical or an hydroxylated C3- C6 alkyl radical, R2 and R3, identical or different, represent H or a C1-C4 alkyl radical, or R2 and R3 are linked together to form a saturated or unsaturated cycle or a heterocycle having 5 or 6 elements, E is a C1-C5 alkyl spacer, R4 and R5, identical or different, represent saturated or unsaturated, linear or branched, C10-C36 hydrocarbon or fluorocarbon chains, optionally comprising C3-C6 cycloalkyle, A- is a biocompatible anion. The invention relates to compositions active for oligonucleotides delivery into eukaryotic cells in culture, ex vivo or in vivo. The invention relates to compositions of transfection comprising an oligonucleotide active for RNA interference. Such compositions can be used as tools for biological studies or as drugs for therapies.

La présente invention concerne des compositions de transfection comprenant un oligonucléotide et une molécule cationique amphiphile de formule (I), dans laquelle - X est N-R1, S ou O, R1 étant un radical alkyle C1-C4 ou un radical alkyle C3- C6 hydroxylé, R2 et R3, identiques ou différents, représentent H ou un radical alkyle C1-C4, ou R2 et R3 sont liés ensemble pour former un cycle saturé ou insaturé ou un hétérocycle présentant 5 ou 6 éléments, E est un espaceur alkyle C1-C5, R4 et R5, identiques ou différents, représentent des chaînes fluorocarbonées ou d'hydrocarbure C10-C36 saturées ou insaturées, linéaires ou ramifiées, comprenant éventuellement un cycloalkyle C3-C6, et A- est un anion biocompatible. L'invention concerne également des compositions actives pour l'apport d'oligonucléotides dans des cellules eucaryotes en culture, ex vivo ou in vivo. L'invention concerne en outre des compositions de transfection comprenant un oligonucléotide actif pour interférence ARN. De telles compositions peuvent être utilisées en tant qu'outils dans des études biologiques ou en tant que médicaments dans des thérapies.

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