Pharmaceutical composition

C - Chemistry – Metallurgy – 12 – N

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Details

C12N 15/11 (2006.01) A61K 31/713 (2006.01) A61P 35/00 (2006.01) C07H 21/02 (2006.01)

Patent

CA 2648132

The invention provides pharmaceutical compositions comprising short single stranded oligonucleotides, of length of between 8 and 17 nucleobases which are complementary to human microRNAs. The short oligonucleotides are particularly effective at alleviating miRNA repression in vivo. It is found that the incorporation of high affinity nucleotide analogues into the oligonucleotides results in highly effective anti-microRNA molecules which appear to function via the formation of almost irreversible duplexes with the miRNA target, rather than RNA cleavage based mechanisms, such as mechanisms associated with RNaseH or RISC.

L'invention concerne des compositions pharmaceutiques comprenant des oligonucléotides monocaténaires courts, d'une longueur comprise entre 8 et 17 nucléobases qui sont complémentaires aux microARNm humains. Les oligonucléotides courts sont notamment efficaces pour atténuer la répression d'ARNmi in vivo. Il a été démontré que l'incorporation d'analogues de nucléotides à affinité élevée dans les oligonucléotides débouche sur des molécules d'anti-microARN très efficaces qui agissent par le biais de la formation de duplexes presque irréversibles avec la cible d'ARNmi plutôt que de mécanismes basés sur le clivage d'ARN, tels que des mécanismes liés à RNaseH ou RISC.

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