Roche Innovation Center Copenhagen A/s

Santaris Pharma A/s

Other

Joacim Elmén

Henrik Frydenlund Hansen

Sakari Kauppinen

Morten Lindow

Susanna Obad

Markus Heidenblad

Phil Kearney

Troels Koch

Henrik Orum

Claes Wahlestedt

Zicai Liang

Anders M Sorensen

Henrik Ørum

Anders Malling Sørensen

Anders Sorensen

The present invention relates to very short heavily modified oligonucleotides which target and inhibit microRNAs in vivo, and their use in medicaments and pharmaceutical compositions.

Micromirs

MICROMIRs

The present invention is directed to novel double-stranded short interfering (siRNA) analogs comprising locked nucleic acid (LNA) monomers. Such compounds induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). The compounds disclosed herein has improved properties compared to non-modified siRNAs and may, accordingly, be useful as therapeutic agents, e.g., in the treatment of various cancer forms. More particularly, the present invention is directed to siRNA analogs comprising a sense strand and an antisense strand, wherein each strand comprises 12-35 nucleotides and wherein the siRNA analogs comprise at least one locked nucleic acid (LNA) monomer.

Short interfering RNA (siRNA) analogues

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 analogs 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.

Pharmaceutical composition comprising anti-miRNA antisense oligonucleotides

MicromiRs

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.

Antisense oligonucleotides for inhibition of microRNA-21

The present invention relate to the use of a combination of an inhibitor of miR-122 and an inhibitor of VLDL assembly, for the treatment of HCV, hyperlipidemia and hypercholesterolemia.

Combination treatment for the treatment of hepatitis C virus infection

MicroRNAs

Pharmaceutical composition comprising anti-mirna antisense oligonucleotide

Growing community of inventors

Malmö, Sweden

Joacim Elmén