Quark Pharmaceuticals, Inc.

Nitto-denko Corporation

Washington University

Bio-lab, Inc.

Qbi Enterprises Ltd.

Sharon Avkin-Nachum

Elena Feinstein

Igor Mett

Hagar Kalinski

Svetlana Adamsky

Lei Yu

Yoshiro Niitsu

Yasunobu Tanaka

Hirokazu Takahashi

Shai Erlich

Elizabeth C Squiers

Xiaomei Jin

Ning Chen

Jean Hildesheim

Andrew E Gelman

Tirtsa Kleinman

Jean-Christophe Truffert

Leonid Beigelman

Myriam Lefoix

Gerald Mathis

The present application relates to nucleic acid compounds, compositions comprising same and methods of use thereof for treatment of various diseases, disorders and conditions. The compounds are preferably chemically synthesized and modified double-stranded nucleic acid molecules which down regulate expression of a p53 gene.

Double-stranded oligonucleotide molecules targeting p53 and methods of use thereof

The invention relates to modified siRNA compounds which down-regulate target gene expression, to pharmaceutical compositions comprising such compounds and to methods of treating and/or preventing the incidence or severity of various diseases or conditions associated with the genes and/or symptoms associated with such diseases or conditions.

siRNA compounds comprising terminal substitutions

Provided herein are double stranded nucleic acid molecules, compositions comprising same and methods of use thereof for the treatment of a subject wherein expression of DDIT4 is associated with the etiology or progression of a disease or disorder in the subject. The compounds are preferably chemically synthesized and modified dsRNA molecules.

Double-stranded oligonucleotide molecules to DDIT4 and methods of use thereof

Disclosed herein are double stranded RNA molecules which have been modified to exhibit one of the following, increased activity, enhanced nuclease stability, reduced off target activity and or reduced immunogenicity, to pharmaceutical compositions comprising such compounds and to methods of use. Further disclosed is a method for the synthesis of threose nucleic acid phosphoramidites and methods of use thereof.

Double stranded oligonucleotide compounds comprising positional modifications

Provided herein are compositions, methods and kits for modulating expression of target genes, particularly heat shock protein 47 (hsp47). The compositions, methods and kits may include nucleic acid molecules (for example, short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA) or short hairpin RNA (shRNA)) that modulate a gene encoding hsp47, for example, the gene encoding human hsp47. The composition and methods disclosed herein may also be used in treating conditions and disorders associated with hsp47 such as liver fibrosis, pulmonary fibrosis, peritoneal fibrosis and kidney fibrosis.

Modulation of HSP47 expression

Disclosed herein are double-stranded RNA nucleic acid molecules, which include at least one pyrazolotriazine nucleotide analog and have been modified to exhibit one of the following, increased on-target activity, increased target specificity, enhanced nuclease stability, reduced off target activity and/or reduced immunogenicity when compared to an unmodified or similarly modified dsRNA; pharmaceutical compositions comprising such molecules and methods of use thereof in therapy.

Therapeutic oligonucleotides comprising pyrazolotriazine nucleotide analogues

Double-stranded oligonucleotide molecules to P53 and methods of use thereof

Provided herein are sphingolipid-polyalkylamine phosphoramidites, methods of generating sphingolipid-polyalkylamine-oligonucleotide compounds, pharmaceutical compositions comprising such compounds, and to methods of use thereof in treating cancer.

Sphingolipid-polyalkylamine-oligonucleotide compounds

Disclosed herein are therapeutic methods for treating lung diseases, disorders and injury in a mammal, including treatment of acute respiratory distress syndrome (ARDS), acute lung injury, pulmonary fibrosis (idiopathic), bleomycin induced pulmonary fibrosis, mechanical ventilator induced lung injury, chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, bronchiolitis obliterans after lung transplantation and lung transplantation-induced acute graft dysfunction, including treatment, prevention or prevention of progression of primary graft failure, ischemia-reperfusion injury, reperfusion injury, reperfusion edema, allograft dysfunction, pulmonary reimplantation response, bronchiolitis obliterans after lung transplantation and/or primary graft dysfunction (PGD) after organ transplantation, in particular in lung transplantation, comprising down-regulating the TLR2 gene or both the TLR2 gene and TLR4 gene. Provided herein are compositions, methods and kits for treating lung diseases, disorders and injury.

Compositions and methods for treating lung disease and injury

Disclosed herein are double stranded nucleic acid molecules and pharmaceutical compositions comprising same useful in the treatment of, inter alia, acute and chronic inflammation, neuropathic pain, primary graft dysfunction (PGD) after lung transplantation in a subject in need thereof. The compounds are preferably chemically synthesized and modified dsRNA compounds, which down regulate or inhibit expression of Toll like receptor 4.

Oligonucleotide modulators of the toll-like receptor pathway

The present invention provides double-stranded RNA (dsRNA) compounds comprising a sense and antisense strand, wherein at least one strand is conjugated to a moiety comprising a phenyl hydrocarbyl group, pharmaceutical compositions comprising same and uses thereof.

Double-stranded nucleic acid compounds

Disclosed herein are double stranded nucleic acid molecules and pharmaceutical compositions comprising same useful in the treatment of, inter alia, acute and chronic inflammation, neuropathic pain, primary graft dysfunction (PGD) after lung transplantation in a subject in need thereof. The compounds are preferably chemically synthesized and modified dsRNA compounds, which down regulate or inhibit expression of a Toll like receptor genes.

The invention relates to siRNA compounds comprising one non-nucleotide moiety covalently attached to at least one of the sense or antisense strands to down-regulate the expression of human genes. The invention also relates to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier and to methods of treating and/or preventing the incidence or severity of various diseases or conditions associated with the target genes and/or symptoms associated with such diseases or conditions.

Growing community of inventors

Nes Zionna, Israel

Sharon Avkin-Nachum