Enhancement of sirna silencing activity using universal...

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/113 (2010.01) A61K 31/713 (2006.01) C07H 21/02 (2006.01)

Patent

CA 2732229

One aspect of the present invention relates to a double stranded nucleic acid useful as an siRNA, that has a sense strand and an antisense strand relative to a target nucleic acid, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one nucleoside comprising a non-natural nucleobase. Another aspect of the invention relates to a method of gene silencing, comprising administering to a mammal in need thereof a therapeutically effective amount of a double-stranded oligonucleotides containing a sense strand and an antisense strand, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand.

Cette invention concerne dans un de ses aspects un acide nucléique bicaténaire utilisé comme ARNsi, comportant un brin sens et un brin antisens par rapport à un acide nucléique cible, le brin sens contenant une ou plusieurs nucléobases modifiées, ou un ou plusieurs non-appariements avec le brin antisens. Dans un autre aspect, linvention concerne un oligonucléotide monocaténaire comprenant au moins un nucléoside contenant une nucléobase non naturelle. Dans un autre aspect, linvention concerne un procédé dextinction de gène, comprenant ladministration chez un mammifère dune quantité thérapeutiquement efficace dun oligonucléotide bicaténaire contenant un brin sens et un brin antisens, le brin sens contenant une ou plusieurs nucléobases modifiées, ou un ou plusieurs non-appariements avec le brin antisens.

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