Induction of exon skipping in eukaryotic cells

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/11 (2006.01) A61K 31/7088 (2006.01) A61K 48/00 (2006.01)

Patent

CA 2423044

The present invention provides a method for at least in part decreasing the production of an aberrant protein in a cell, said cell comprising pre-mRNA comprising exons coding for said protein, by inducing so-called exon skipping in said cell. Exon-skipping results in mature mRNA that does not contain the skipped exon which leads to an altered product if said exon codes for amino acids. Exon skipping is performed by providing a cell with an agent capable of specifically inhibiting an exon inclusion signal, for instance an exon recognition sequence, of said exon. Said exon inclusion signal can be interfered with by a nucleic acid comprising complementarity to a part of said exon. Said nucleic acid, which is also herewith provided, can be used for the preparation of a medicament, for instance for the treatment of an inherited disease.

La présente invention concerne une méthode qui permet au moins en partie de diminuer la production d'une protéine aberrante dans une cellule, laquelle cellule comprend un pré-ARNm contenant des exons codant pour ladite protéine, par induction d'une soi-disante omission d'exon dans la cellule. L'omission d'exon débouche sur un ARNm mature exempt de l'exon omis et donne un produit modifié lorsque ledit exon code pour des acides aminés. L'omission d'exon s'effectue par la mise en oeuvre d'une cellule qui comprend un agent pouvant inhiber de manière spécifique un signal d'inclusion d'exon (par exemple une séquence d'identification d'exons) de l'exon. Le signal d'inclusion d'exon peut être brouillé par un acide nucléique complémentaire d'une partie de l'exon. L'acide nucléique, également mis en oeuvre, peut être utilisé pour la préparation d'un médicament destiné, par exemple, au traitement d'une maladie héréditaire.

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