Pharmaceutical composition comprising anti-mirna antisense oligonucleotide
The invention provides pharmaceutical compositions comprising short single stranded oligonucleotides, of length of between 8 and 26 nucleobases which are complementary to human microRNAs selected from the group consisting of miR19b, miR21, miR122a, miR155 and miR375. 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. An oligonucleotide that is:
(SEQ ID NO: 59)
5′- c s t s t s c s a s a s t s -3′
wherein:
a lowercase letter identifies a DNA unit;
an upper case bold letter identifies an LNA unit;
m C identifies a 5-methylcytosine LNA;
subscript s identifies a phosphorothioate internucleoside linkage, and the LNA units are beta-D-oxy, as identified by a o superscript after the LNA units.
2. A composition comprising the oligonucleotide according to claim 1 , and a pharmaceutically acceptable diluent, carrier or adjuvant, or combinations thereof.