Constructs for enhancement of gene expression in muscle

Details Constructs for enhancement of gene expression in muscle Constructs for enhancement of gene expression in muscle

C - Chemistry, Metallurgy

12

N

C12N 15/85 (2006.01) A61K 48/00 (2006.01) C07K 14/47 (2006.01) C12N 15/67 (2006.01)

Patent

CA 2684534

Efficient and muscle-specific gene expression can be obtained with constructs containing two or more copies of USE and/or .DELTA.USE fused to the minimal promoter of the TnlSlow gene. USE is a small (about 160-bp) upstream enhancer of the TnlSlow gene that confers slow-twitch muscle fiber specificity. .DELTA.USE is generated from a 100-bp deletion at the 5' end of USE. .DELTA.USE confers expression in slow- and fast-twitch muscle fibers. The strength and relatively small size (less than 600-bp) of these constructs make them useful for gene therapy applications.

Selon l'invention, une expression génétique efficace spécifique d'un muscle peut être obtenue au moyen de constructions contenant au moins deux copies de USE et/ou .DELTA.USE fusionnées au promoteur minimal du gène TnlSlow. USE est un petit amplificateur amont (environ 160-bp) du gène TnlSlow qui confère une spécificité de fibres musculaires à fibrillation lente. .DELTA.USE est produit à partir d'une délétion 100-bp au niveau de l'extrémité 5' de USE. .DELTA.USE confère une expression dans des fibres musculaires à fibrillation lente et rapide. La résistance et la relativement petite taille (inférieure à 600-bp) de ces constructions les rendent utiles dans des applications de thérapie génique.

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