Methods for use in modulating mir-122a

C - Chemistry – Metallurgy – 12 – N

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C12N 15/11 (2006.01) A61K 31/711 (2006.01)

Patent

CA 2620856

Methods are provided for the treatment of cardiovascular or metabolic diseases characterized by elevated serum total cholesterol, elevated serum LDL- cholesterol, or elevated serum triglycerides, through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Further provided are methods for reducing hepatic steatosis or liver tissue triglyceride accumulation through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Such methods employ oligomeric compounds which hybridize with or sterically interfere with nucleic acid molecules comprising or encoding miR-122a. Such oligomeric compounds may include one or more modifications thereon, which may improve the activity, stability, or nuclease resistance of the oligomeric compound. These modified oligomeric compounds are used as single compounds or in compositions, including pharmaceutical compositions, to modulate or mimic the targeted nucleic acid comprising or encoding miR-122a.

L'invention concerne des méthodes de traitement de maladies cardio-vasculaires ou métaboliques caractérisées par un cholestérol total dans le sérum élevé, un cholestérol LDL dans le sérum élevé ou des triglycérides dans le sérum élevés, consistant à administrer un composé oligomère, lequel module les taux ou l'activité de miR-122a. De plus, l'invention concerne des procédés permettant de réduire la stéatose hépatique ou une accumulation de triglycérides dans les tissus du foie par administration d'un composé oligomère, lequel module les taux ou l'activé de miR-122a. De tels procédés mettent en oeuvre des composés oligomères s'hybridant ou interférant de manière stérique avec des molécules d'acide nucléique comprenant ou codant miR-122a. De tels composés oligomères peuvent comprendre une ou plusieurs modifications, lesquelles peuvent améliorer l'activité, la stabilité ou la résistance à la nucléase du composé oligomère. Ces composés oligomères modifiés sont utilisés comme composés uniques ou dans des compositions, notamment des compositions pharmaceutiques, aux fins de modulation et d'imitation de l'acide nucléique ciblé comprenant ou codant miR-122a.

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