Nucleic acid compounds for inhibiting ras gene expression...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/11 (2006.01) A61K 31/713 (2006.01)

Patent

CA 2679388

The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing RAS (e.g., HRAS, KRAS, NRAS) gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to an HRAS, KRAS, or NRAS mRNA. In addition, the meroduplex may have at least one uridine is a 5-methyluridine, a nucleoside is a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of a RAS gene in a cell or in a subject to treat a RAS-related disease.

L'invention concerne des molécules d'acide ribonucléique méroduplex (ARNmd) pouvant diminuer ou étouffer l'expression du gène RAS (par exemple, HRAS, KRAS, NRAS). Un ARNmd de cette description comprend au moins trois brins qui s'associent pour former au moins deux régions double brin non chevauchantes séparées par une encoche ou un espace dans lequel un brin est complémentaire à un ARNm HRAS, KRAS ou NRAS. De plus, le méroduplex peut avoir au moins une uridine qui est une 5-méthyluridine, un nucléoside qui est un acide nucléique bloqué, ou éventuellement d'autres modifications, et toute combinaison de ceux-ci. Sont également proposés des procédés de diminution de l'expression d'un gène RAS dans une cellule ou chez un sujet pour traiter une maladie liée au RAS.

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