PHARMACEUTICAL COMPOSITIONS COMPRISING ANTI-MIRNA ANTISENSE OLIGONUCLEOTIDES

摘要

The invention provides oligonucleotides 8 - 22 nucleotides in length, for inhibition of a microRNA target in a cell, which comprise a high proportion of high affinity nucleotide analogue units as well as LNA units. The 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.