Roche Innovation Center Copenhagen A/s

Roche Diagnostics Gmbh

Santaris Pharma A/s

Pna Diagnostics A/s

Other

Georgia Tech Research Corporation

Boehringer Mannheim Gmbh

Henrik Orum

Henrik Frydenlund Hansen

Troels Koch

Christopher John Stanley

Ellen Marie Straarup

Hans-Georg Batz

Jacob Ravn

Claes Wahlestedt

Joacim Elmén

Nanna Albaek

Susanne Kammler

Zicai Liang

Gregroy Hardee

Mikkel Jorgensen

Anders M Sorensen

Danith H Ly

Charlotte Albaek Thrue

Majken Westergaard

Maj Hedtjärn

Niels Fisker Nielsen

Miriam Frieden

Marie Wickstrom Lindholm

Gerd Haberhausen

Jens Bo Rode Hansen

Bruce Alan Armitage

Gary B Schuster

Jens Bo Hansen

Christoph Kessler

Knut Bartl

Bruce A Armitage

Gary B Shuster

Ole Basboll

Mikkell Jorgensen

Joacim Elmen

Anders Malling Sorensen

Maj HEDTJÄRN

The invention relates to the field of oligonucleotide therapeutics, and in particular to the use of a cleavable, e.g. a phosphodiester region covalently attached to a conjugate, a targeting group or blocking group to enhance the properties of the oligonucleotides, for example to improve the therapeutic index.

Oligonucleotide conjugates

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 for LNA oligomers, for the treatment of a metabolic or liver disorder, wherein the LNA oligomer is administered orally in a unit dose of less than 50 mgs/kg, wherein the LNA oligomer is administered in the presence of a penetration (permeation) enhancer.

Oral delivery of therapeutically effective LNA oligonucleotides

The invention provides LNA gapmer oligomers of between 10-20 nucleobases in length, which have a total of 1-3 phosphodiester internucleoside linkages. Such oligomers have been found to have superior bioavailability and have also been found to selectively accumulate in kidney cells.

Short oligomer antagonist compounds for the modulation of target mRNA

The present invention provides improved oligomeric compound, in particular oligonucleotide compounds, and methods for modulating the expression of the Bcl-2 gene in humans. In particular, this invention relates to oligomeric compounds of 10-30 nucleobases in length which comprise a target binding domain that is specifically hybridizable to a region ranging from base position No. 1459 (5') to No. 1476 (3&#x2032;) of the human Bcl-2 mRNA, said target binding domain having the formula: 5&#x2032;-[(DNA/RNA)-(LNA/LNA*)-(DNA/RNA/LNA*)-(LNA/LNA*)-(DNA/RNA)]-3&#x2032; and said target binding domain comprising at least two LNA nucleotides or LNA analogue nucleotides linked by a phosphorothioate group (&#x2014;O&#x2014;P(O,S)&#x2014;O&#x2014;). In particular the oligo is predominantly or fully thiolated. The invention also provides the use of such oligomers or conjugates or chimera for the treatment of various diseases associated with the expression of the Bcl-2 gene, such as cancer.

Oligomeric compounds for the modulation of Bcl-2

Method for the detection of a nucleic acid comprising the production of a plurality of amplificates of a section of this nucleic acid with the aid of two primers, one of which can bind to a binding sequence A of the nucleic acid and the other can bind to a binding sequence C' which is complementary to a sequence C which is located in the 3&#x2032; direction from A and does not overlap with A, contacting the amplificates with a probe having a binding sequence D which can bind to a sequence B which is located between the sequences A and C or to the complement thereof, and detecting the formation of a hybrid of the amplificate and probe where the sequence located between the binding sequences A and C contains no nucleotides that do not belong to the binding sequence D of the probe or its complement D&#x2032;.

Specific and sensitive nucleic acid detection method

A nucleic acid analog comprising a polymeric strand which includes a sequence of ligands bound to a backbone made up of linked backbone moieties, which analog is capable of hybridization to a nucleic acid of complementary sequence, further comprising a chelating moiety capable of binding at least one metal ion by chelation.

Nucleic acid analogs with a chelating functionality

New electron transfer moiety labeled nucleic acid analogue probes are provided that can be used in methods for determining nucleic acids in a sample. The new probes can be prepared using novel monomer subunits in a chemical synthesis route. The nucleic acids can be determined by binding the probe molecules to the nucleic acid and inducing electron transfer within the complex formed. The occurrence of the electron transfer is determined as a measure of the nucleic acid.

Method for determining a nucleic acid

PNA monomers with electron donor or acceptor

A selected region of a nucleic acid is protected from attach by nuclease by completing to the nucleic acid a nucleic acid analogue of the PNA type. The surviving sequence may be detected in an assay, optionally after amplification. A PCR reaction may be sterilized and its product assayed by protecting a characterizing region of the product by PNA hybridization followed by nuclease degradation of unprotected nucleic acid.

Protecting nucleic acids and methods of analysis

A nucleic acid analog comprising a polymeric strand which includes a sequence of ligands bounds to a backbone made up of linked backbone moieties, which analog is capable of hybridization to a nucleic acid of complementary sequence, further comprising a chelating moiety capable of binding at least one metal ion by chelation.

Methods of capturing nucleic acid analogs and nucleic acids on a solid

Growing community of inventors

Vaerlose, Denmark

Henrik Orum