Treating hepatitis c virus infection with over-expression of...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/113 (2010.01) A61K 31/713 (2006.01) A61P 31/14 (2006.01)

Patent

CA 2739948

The present invention is directed to methods of treating cells infected with HCV and mammals suffering from HCV infection by transfecting the infected cells with miRNA-196 mimic. miRNA- 196 mimic significantly down-regulates Bach1 protein and HCV gene expression, while also up-regulating HMOX1 gene expression. miRNA-196 binds with the 3'-UTR of Bach1 mRNA to reduce the expression of Bach1. As such, miRNA-196 can play an important role in the regulation of HCV replication and HMOX1/Bach1 expression in hepatocytes. The present invention also provides a formulation for the treatment of cells expressing HCV comprising a therapeutically effective amount of miRNA-196 such that Bach1 and HCV gene expression are down- regulated while HMOX1 expression is increased. The formulations are adapted to enable the transfection of miRNA-196 mimic into hepatocytes expressing HCV proteins.

L'invention concerne des méthodes de traitement de cellules infectées par le VHC et de mammifères souffrant de l'infection due au VHC par transfection des cellules infectées avec un mime de miARN-196. Le mime de miARN-196 régule significativement à la baisse l'expression de la protéine Bach1 et du gène du VHC, tout en régulant à la hausse l'expression du gène HMOX1. Le miARN-196 se lie à la séquence non traduite 3' de l'ARNm Bach1 pour réduire l'expression de Bach1. En tant que tel, le miARN-196 peut jouer un rôle important dans la régulation de la réplication du VHC et dans l'expression de HMOX1/Bach1 dans les hépatocytes. L'invention concerne également une formulation pour le traitement de cellules exprimant le VHC renfermant une quantité thérapeutiquement efficace de miARN-196 permettant de réguler à la baisse l'expression de Bach1 et du gène du VHC, tout en augmentant l'expression de HMOX1. Les formulations sont adaptées pour permettre la transfection de l'analogue de miARN-196 dans les hépatocytes exprimant des protéines du VHC.

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