Induction of methylation of cpg sequences by dsrnas in...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/11 (2006.01) C12N 5/10 (2006.01)

Patent

CA 2517259

It is clarified that a synthetic short interfering RNA (siRNA) targeting a CpG island-containing domain on a gene promoter specifically induces the methylation of CpG in the target region or the neighborhood thereof in a human cell. The methylation of the promoter regulates the expression of a gene encoded by the downstream thereof at the transcriptional level. Thus, it is intended to provide a method of inducing DNA methylation with the use of an siRNA and a method of regulating gene expression via the methylation of a promoter by the siRNA. It is also intended to provide a DNA methylation inducer or a gene expression regulator containing the above siRNA or a vector expressing this siRNA or dsRNA.

Il est évident qu'un ARN de courte interférence (ARNsi) synthétique ciblant un domaine contenant un îlot CpG sur un gène promoteur induit de manière spécifique la méthylation du CpG dans la région cible ou dans le voisinage de celui-ci dans une cellule humaine. La méthylation du promoteur assure la régulation de l'expression d'un gène codé par le côté aval de celui-ci au niveau transcriptionnel. Ainsi, l'invention vise à fournir un procédé d'induction de méthylation d'ADN au moyen d'un ARNsi et un procédé de régulation de l'expression génétique via la méthylation d'un promoteur par l'ARNsi. L'invention vise également à fournir un inducteur de méthylation d'ADN ou un régulateur de l'expression génétique contenant ledit ARNsi ou un vecteur exprimant un tel ARNsi ou ARNds.

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