Restoration of visual responses by in vivo delivery of...

A - Human Necessities – 61 – K

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A61K 48/00 (2006.01) A61P 27/02 (2006.01) C07K 14/705 (2006.01) C12N 15/85 (2006.01) C12N 15/864 (2006.01)

Patent

CA 2685900

Nucleic acid vectors encoding light-gated cation-selective membrane channels, in particular channelrhodopsin-2 (Chop2), converted inner retinal neurons to photosensitive cells in photoreceptor- degenerated retina in an animal model. Such treatment restored visual perception and various aspects of vision. A method of restoring light sensitivity to a retina of a subject suffering from vision loss due to photoreceptor degeneration, as in retinitis pigmentosa or macular degeneration, is provided. The method comprises delivering to the subject by intravitreal or subretinal injection, the above nucleic acid vector which comprises an open reading frame encoding a rhodopsin, to which is operatively linked a promoter and transcriptional regulatory sequences, so that the nucleic acid is expressed in inner retinal neurons. These cells, normally light-insensitive, are converted to a light-sensitive state and transmit visual information to the brain, compensating for the loss, and leading to restoration of various visual capabilities.

Des vecteurs d'acide nucléique codant pour des canaux membranaires photo-dépendants sélectifs des cations, notamment la channelrhodopsine-2 (Chop2), ont transformé des neurones rétiniens internes en cellules photosensibles chez un modèle animal dont les photorécepteurs de la rétine ont dégénéré. Ce type de traitement a restauré la perception visuelle et divers aspects de la vision. On propose un procédé pour restaurer la photosensibilité de la rétine d'un sujet souffrant d'une perte de vision due à la dégénérescence des photorécepteurs, comme dans le cas de la rétinite pigmentaire ou de la dégénérescence maculaire. Le procédé comprend l'administration par voie intravitréenne ou sous-rétinienne au sujet du vecteur d'acide nucléique ci-dessus qui comprend un cadre ouvert de lecture codant pour une rhodopsine, auquel est lié de manière fonctionnelle un promoteur et des séquences régulatrices de la transcription, de sorte que l'acide nucléique est exprimé dans les neurones rétiniens internes. Ces cellules, normalement non photosensibles, sont transformées en cellules photosensibles et transmettent des informations visuelles au cerveau, ce qui compense la perte et conduit à la restauration de diverses capacités visuelles.

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