PROBLEM TO BE SOLVED: To provide pharmaceutical compositions comprising short single stranded oligonucleotides, of length of between 8 and 26 nucleobases which are complementary to human miRNAs.SOLUTION: The short oligonucleotides selected from the group consisting of miR19b, miR21, miR122a, miR155 and miR375 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-miRNA molecules which appear to function via the formation of almost irreversible duplexes with a miRNA target, rather than RNA cleavage-based mechanisms, such as mechanisms associated with RNaseH or RISC.COPYRIGHT: (C)2013,JPO&INPIT【課題】ヒトミクロRNAと相補的な長さ8~26核酸塩基の短い一本鎖オリゴヌクレオチドを含む医薬組成物を提供する。【解決手段】miR19b、miR21、miR122a、miR155、およびmiR375からなる群から選ばれる該短いオリゴヌクレオチドは、in vivoでmiRNAの抑制を緩和するのに特に有効である。高親和性ヌクレオチド類似体の該オリゴヌクレオチドへの組み込みは、RNA開裂に基づく機序、例えばRNアーゼHまたはRISCに関連する機序ではなくmiRNA標的とのほぼ不可逆的な二本鎖の形成を介して機能する有効性の高い抗ミクロRNA分子をもたらす。【選択図】なし
