Pharmaceutical Composition for Inhibition of Disease-inducing microRNAs

Abstract

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.

1 - 95 . (canceled) 
     
     
         96 . A method for reducing the effective amount of a miRNA target in a cell or an organism, comprising administering a single stranded oligonucleotide having a length of between 8 and 17 nucleobase units to the cell or organism thereby reducing the effective amount of the miRNA target in the cell; wherein the single stranded oligonucleotide is complementary to a human microRNA; wherein the single stranded oligonucleotide comprises at least 3 LNA units in a region which is complementary to the microRNA seed region; and wherein the single stranded oligonucleotide does not comprise region of more than 3 consecutive DNA units.