Methods of gene therapy for treating disorders of the ear by...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/86 (2006.01) A61K 48/00 (2006.01) A61P 27/00 (2006.01) C12N 15/861 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2514781

The invention is directed to a method of changing the sensory perception of an animal. The method comprises administering an expression vector comprising a nucleic acid sequence encoding an atonal-associated factor, which is expressed to produce the atonal-associated factor resulting in generation of hair cells that allow perception of stimuli in the inner ear. Also provided is a method of generating a hair cell in differentiated sensory epitheliain vivo. The method comprises contacting differentiated sensory epithelial cells with an adenoviral vector (a) deficient in one or more replication-essential gene functions of the El region and E4 region, (b) comprising a spacer in the E4 region, and (c) comprising a nucleic acid sequence encoding an atonal- associated factor. The nucleic acid sequence is expressed to produce the atonal-associated factor such that a hair cell is generated. An adenoviral vector encoding an atonal-associated factor also is provided.

L'invention concerne un procédé permettant de changer la perception sensorielle d'un animal. Ce procédé consiste à administrer un vecteur d'expression contenant une séquence d'acide nucléique codant un facteur atonal, qui est exprimé afin de produire le facteur atone, ce qui permet de générer des cellules ciliées permettant la perception de stimuli dans l'oreille interne. L'invention porte aussi sur un procédé de génération d'une cellule ciliée dans des épithéliums sensoriels différentiés in vivo. Ce procédé consiste à mettre en contact des cellules épithéliales sensorielles différentiées avec un vecteur adénoviral (a) déficient en une ou plusieurs fonctions géniques essentielles pour le réplication de la zone E1 et E4, (b) comprenant un espaceur dans la zone E4, et (c) comprenant une séquence d'acide nucléique codant un facteur atonal. Cette séquence d'acide nucléique est exprimée afin de produire le facteur atonal de manière à générer une cellule ciliée. L'invention concerne aussi un vecteur adénoviral codant un facteur atonal.

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