Abstract: Aptamers and improved aptamers are provided with enhanced efficacy for binding to target molecules in vivo or for treating cancer or other diseases. Such improvements in aptamers are provided that enhance in vivo efficacy such as binding to the target molecule or enhancing anti-cancer activity. Such improvements also include stability to serum nucleases, reduced binding to a soluble form of the target molecule, increased avidity, affinity or specificity to the target molecule on a cell surface, increased lifetime in circulation, or any combination of the foregoing. Improvements are provided by truncation, multimerization, including at least one non-natural nucleic acid, adding a 3? or 5? polyethylene glycol, or any combination thereof. Aptamers for treatment of autoimmune diseases are also provided.

Abstract: The current invention provides an improved oligonucleotide and its use for treating, ameliorating, preventing, delaying and/or treating a human cis-element repeat instability associated genetic neuromuscular or neurodegenerative disorder.

Abstract: As a means for solving the problem of providing a nucleic acid conjugate that does not undergo degradation at a DNA-RNA bonding site even in vivo, provided is a nucleic acid conjugate comprising a single-stranded DNA and a double-stranded RNA, wherein the 3? position of the 3?-terminal deoxyribonucleotide residue of the single-stranded DNA is bonded to the 5? position of the 5?-terminal ribonucleotide residue of one of the ribonucleotide strands of the double-stranded RNA, and the hydroxyl group at the 2? position of the 5?-terminal nucleotide of the ribonucleotide strand, which is bonded to the single-stranded DNA, is substituted with an alkoxy group or a halogen atom, and/or the phosphate diester group between the 3? position of the first ribonucleotide bonded to the single-stranded DNA and the 5? position of the adjacent ribonucleotide is substituted with any of phosphorothioate group, dithiophosphate diester group and trithiophosphate diester group.

Abstract: The present invention is based in part on the discovery of brown and white fat cell specific surface markers. It has been found that the small amino acid transporter Slca10/Asc1 is a specific surface marker for white adipocytes and that the ligand-gated ion channel P2X5 and the small amino acid transporter Slc36a2 are specific surface markers for brown adipocytes. Having identified these specific white and brown cell surface markers, the present invention provides compositions and methods suitable for the targeting of any number of agents to a white or brown adipose tissue and the identification and isolation of white or brown adipocytes for any number of uses including therapeutic, screening and diagnostic purposes.

Abstract: The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

Abstract: The present invention relates to the field of cardiology. More specifically, the present invention provides methods and compositions for inducing proliferation of cardiomyocytes. In a specific embodiment, a method for inducing proliferation of cardiomyocytes comprises the step of administering an effective amount of an ALMS1 inhibitor.

Abstract: This invention provides recombinant DNA constructs and methods for manipulating expression of a target gene that is regulated by a small RNA, by interfering with the binding of the small RNA to its target gene. More specifically, this invention discloses recombinant DNA constructs encoding cleavage blockers, 5-modified cleavage blockers, and translational inhibitors useful for modulating expression of a target gene and methods for their use. Further disclosed are miRNA targets useful for designing recombinant DNA constructs including miRNA-unresponsive transgenes, miRNA decoys, cleavage blockers, 5-modified cleavage blockers, and translational inhibitors, as well as methods for their use, and transgenic eukaryotic cells and organisms containing such constructs.

Abstract: The invention provides an improved design for the construction of extensible nucleic acid-based, ligand-controlled regulatory systems, and the nucleic acid regulatory systems resulting therefrom. The invention contemplates improving the design of the switches (ligand-controlled regulatory systems) through the design of an information transmission domain (ITD). The improved ITD eliminates free-floating ends of the switching and the competing strands, and localizes competitive hybridization events to a contiguous strand of competing and switching strands in a strand-displacement mechanism-based switch, thereby improving the kinetics of strand-displacement. The improved regulatory systems have many uses in various biological systems, including gene expression control or ligand-concentration sensing.

Abstract: The present invention relates to oligomer compounds (oligomers) for the treatment and prevention of acute myeloid leukemia, which target GLI2 mRNA in a cell, leading to reduced expression of GLI2.

Abstract: The invention relates to design of short oligonucleotides and analogs thereof (such as, di-, and trinucleotide compounds) useful for various therapeutic applications. It is believed that the compounds of the invention can be used as antiviral agents, anticancer agents and so on. In certain embodiments, the compounds of the invention can modulate immune-stimulatory pathways and non-TLR pathways. The invention also relates to design modified oligonucleotides for therapeutic applications, by excluding nucleotide segments having off-target effects from the modified oligonucleotides. In another aspect, the invention provides pharmaceutical compositions including one or more compounds of the invention. It is believed that the compounds and compositions as described herein have therapeutic utility against a variety of diseases, including viral diseases, autoimmune diseases (such as, allergy, asthma, and inflammatory disorders) and cancer.

Abstract: RNA interference is provided for inhibition of Frizzled Related Protein-1 mRNA expression, in particular, for treating patients having glaucoma or at risk of developing glaucoma.

Abstract: Oligonucleotide compounds modulate expression and/or function of Vascular Endothelial Growth Factor (VEGF) polynucleotides and encoded products thereof. Methods for treating diseases associated with Vascular Endothelial Growth Factor (VEGF) comprise administering one or more Oligonucleotide compounds designed to inhibit the VEGF natural antisense transcript to patients.

Abstract: The present invention relates to novel methods for the prevention, treatment and diagnosis of Alzheimer's disease. In addition, the invention relates to methods for assessing an individual's susceptibility or pre-disposition to Alzheimer's disease. The methods of the present invention involve the use of therapeutic targets and diagnostic and/or predictive markers within the mTOR signalling pathway. The methods also involve screening subjects for genetic polymorphisms associated with rapamycin-sensitive genes.

Abstract: Disclosed herein are methods of controlling insect pests, in particular Leptinotarsa spp. which infest crop plants, and methods of providing plants resistant to such pests. Also disclosed are polynucleotides and recombinant DNA molecules and constructs useful in such methods, insecticidal compositions such as topical sprays containing insecticidal double-stranded RNAs, and solanaceous plants with improved resistance to infestation by Leptinotarsa spp. Further disclosed are methods of selecting target genes for RNAi-mediated silencing and control of Leptinotarsa spp.

Abstract: Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19-23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3? ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.

Abstract: There is provided a method of treating an inflammatory response to infection and complications associated therewith, by administering a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor to a subject, in need thereof. There is also provided a method of treating or preventing treating or preventing renal failure; renal dysfunction; respiratory failure; respiratory dysfunction; or acute lung injury. Provided herein are uses, pharmaceutical compositions, and commercial packages associated therewith.

Abstract: In certain embodiments, the present invention provides oligomeric compounds having favorable toxicity profiles and therapeutic indexes. Compounds of the present invention comprise bicyclic nucleosides. Certain such bicyclic nucleosides are pyrimidines that do not include a methyl group at the 5-carbon. Oligomeric compounds comprising such nucleosides are less toxic than compounds comprising bicyclic nucleosides that do include a methyl group at the 5-carbon. In certain embodiments, the present invention provides methods of preparing and using such compounds.

Abstract: Provided are 9-base morpholino antisense compounds targeted to polyCUG repeats in the 3?UTR region of dystrophia myotonica protein kinase (DMPK) mRNA, and related methods for treating myotonic dystrophy DM1.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of GCCR mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof.

Abstract: Described are compositions and methods useful for modulating the immune system of a subject. Also included are diagnostic methods for monitoring an immunologic condition. In particular the invention relates to antagonists of interferon proteins and associated methods of use as well as methods to develop neutralizing antibodies against IFN antagonists to treat viral infections.

Abstract: The present invention is related to an L nucleic acid that binds to an SDF-1.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of PTP1B mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate metabolic disease, for example, diabetes, or a symptom thereof.

Abstract: Medical devices comprising an anti-connexin agent suitable for introduction into a subject.

Abstract: The present invention concerns a TCTP antagonist, in particular a nucleic acid targeting an m RNA encoding Translationally-Controlled Tumor Protein (TCTP), wherein said nucleic acid is capable of reducing the amount of TCTP in cells, for use in the treatment or prevention of hormone-independent cancer or chemo-resistant cancer, such as an androgen-independent prostate cancer.

Abstract: An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

Abstract: Provided are novel methods and compositions for the modulation of thermogenesis. Such methods are particularly advantageous in that they allow for the reduction of body fat in a subject without the subject having to adjust their caloric intake through dieting, modify their physical activity or undergo bariatric surgery. Accordingly, the methods of the invention are particularly useful for treating or preventing obesity. Also provided are methods of screening for novel agents that modulate the activity of thermogenic regulators.

Abstract: In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG. 1A). Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle. In yet a further aspect, the invention provides methods for expression of a small RNA molecule within a cell, such as an siRNA capable of downregulating CCR5, wherein expression of the small RNA molecule is relatively non-cytotoxic to the cell. The invention also includes small RNA molecules, such as an siRNA capable of downregulating CCR5, that are relatively non-cytotoxic to cells.

Abstract: The present invention provides compositions and methods of treatment of HCV infected subjects that are not sensitive to interferon treatment. Further, compositions and methods are provided for prevention of organ transplant rejection. The compositions of the invention comprise an anti microRNA-122 oligonucleotide, and are made for administration to a primate.

Abstract: The present invention provides compositions comprising therapeutic nucleic acids such as interfering RNA (e.g., dsRNA such as siRNA) that target SMAD4 gene expression, lipid particles comprising one or more (e.g., a cocktail) of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for treating anemia of inflammation in humans).

Abstract: The invention provides therapeutic and prophylactic compounds and methods for altering the activity of pyruvate dehydrogenase kinase (e.g. PDK1, PDK2, PDK3, PDK4). Such therapies are useful for the treatment of neoplasia. The invention further provides therapeutic and prophylactic compounds and methods of altering pyruvate dehydrogenase activity to treat or prevent cell death related to ischemia.

Abstract: This disclosure relates to manipulating microRNA for the management of neurological disorders and compositions related thereto. In certain embodiments, the disclosure contemplates inhibition of miR324 or miR324-5p, e.g., the use of nucleobase polymers for antisense disruptions or RNA interference of miR-324 expression or for miR324-5p binding in order to increase Kv4.2 expression. In certain embodiments, the disclosure relates to methods of treating or preventing a neurological disease or condition comprising administering an effective amount of an inhibitor to a subject in need thereto.

Abstract: The present invention relates to methods, kits and compositions to treat hypertension and other cardiovascular diseases in a subject, in particular, a method of treating or preventing a cardiovascular disease in a subject comprising administering to a subject at least one anti-miR agent to miRNA-425. In some embodiments, an anti-miR agent is a small molecule or an oligonucleotide complementary to at least part of the miR-425 of SEQ ID NO: 1, or an anti-miR complementary to at least part of the miRNA seed sequence AUGACA (SEQ ID NO: 2). Another aspect of the present invention relates to methods, kits and compositions to treat low blood pressure in a subject comprising administering a composition comprising a miR-425 agent to decrease ANP levels in the subject.

Abstract: The present invention relates to a method for producing pools of siRNA molecules suitable for RNA interference.

Abstract: It is an object of the instant invention to provide a method for the rapid evaluation of novel sugar modifications to be used in siRNA synthesis including the rapid evaluation of chemical modification patterns within the siRNA to effectuate increased stability and ultimately increased efficacy of a siRNA therapeutic. It is a further object of the instant invention to provide novel nucleosides useful for siRNA therapy.

Abstract: The present invention provides a method for diagnosing and detecting diseases associated with pancreas. The present invention provides one or more proteins or fragments thereof, peptides or nucleic acid molecules differentially expressed in pancreatic diseases (PCAT) and antibodies binds to PCAT. The present invention provides that PCAT is used as targets for screening agents that modulates the PCAT activities. Further, the present invention provides methods for treating diseases associated with pancreas.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Discs large homolog (DLG), in particular, by targeting natural antisense polynucleotides of Discs large homolog (DLG). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorder associated with the expression of DLG.

Abstract: The present invention discloses gene targets, constructs and methods for the genetic control of plant disease caused by nematodes of the genus Pratylenchus (root lesion nematodes). The present invention relates to achieving a plant protective effect through the identification of target coding sequences and the use of recombinant DNA technologies for post-transcriptionally repressing or inhibiting expression of the target coding sequences in the cells of plant-parasitic nematodes. The disclosed gene targets are conserved and expected to be essential and sensitive to RNAi perturbation in different Pratylenchus species, facilitating genus-wide targeting by RNA interference.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting Glycogen Synthase Kinase-3 (GSK-3), and methods of using the dsRNA to inhibit expression of GSK-3.

Abstract: The invention relates to lipid formulated double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a gene from the Ebola virus.

Abstract: The present invention relates generally to synthetic genes for modifying endogenous gene expression in a cell, tissue or organ of a transgenic organism, in particular a transgenic animal or plant. More particularly, the present invention provides novel synthetic genes and genetic constructs which are capable of repressing delaying or otherwise reducing the expression of an endogenous gene or a target gene in an organism when introduced thereto.

Abstract: This disclosure provides purified nucleic acids and polypeptides. Also provided are transgenic plants, seeds, and plant cells containing DNA for expression of the proteins that are useful for imparting enhanced agronomic trait(s) to transgenic crop plants, methods of making such plants and methods of making agricultural commodity including seeds and hybrid seeds from such plants.

Abstract: Compositions and methods are provided for sensitizing neoplastic cells to radiotherapy. The invention provides aptamer-inhibitory nucleic acid chimeras that selectively inliibit the expression of radiosensitizing genes in neoplastic cells expressing a cell surface molecule that binds the aptamer.

Abstract: The invention provides compositions and methods for signal activated RNA interference (saRNAi), preferably in vivo. The invention provides polynucleotides that switches between an inactive form and an active form upon covalent or non-covalent interaction with one or more specific chemical signals, such as disease-specific mRNA, miRNA, or other cellular RNA products with sequences that characterize diseased states of the cell. The interaction between the subject polynucleotides and the signals is preferably mediated by hybridization, which exposes, facilitates the formation, and/or allows the formation of a substrate that can be processed by proteins of the RNAi pathway (such as Dicer). The input and output of multiple different polynucleotides of the invention can form an in vivo signaling network. In addition, the multiple input signals can be integrated to modulate the activity of the subject polynucleotides.

Abstract: Connexin modulation for the treatment of wounds that do not heal at expected rates, including delayed healing wounds, incompletely healing wounds, and chronic wounds, and associated methods, compositions and articles.

Abstract: Polynucleotides and polypeptides which participate in influenza virus infection of cells and nucleic acid molecules, which include a polynucleotide sequence capable of specifically binding the polypeptides of the present invention. Also provided are methods of using such nucleic acid molecules, polynucleotides and antibodies directed thereagainst for diagnosing, treating and preventing influenza virus infection.

Abstract: The present invention relates to methods for controlling pest infestation using double stranded RNA molecules. The invention provides methods for making transgenic plants that express the double stranded RNA molecules, as well as pesticidal agents and commodity products produced by the inventive plants.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Tumor Protein 63 (p63), in particular, by targeting natural antisense polynucleotides of Tumor Protein 63 (p63). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of p63.

Abstract: The present invention provides a method for diagnosing and detecting diseases associated with colon. The present invention provides one or more proteins or fragments thereof, peptides or nucleic acid molecules differentially expressed in colon diseases (CCAT) and antibodies binds to CCAT. The present invention provides that CCAT is used as targets for screening agents that modulates the CCAT activities. Further the present invention provides methods for treating diseases associated with colon.

Abstract: Provided herein are methods for inhibiting expression of DOHH in a cell, and for inhibiting hypusination of eIF5A in a cell, the methods comprising contacting a cell with a miRNA or a nucleic acid molecule encoding the miRNA, wherein the miRNA binds to the 3?UTR of the DOHH mRNA and wherein binding results in a reduction in DOHH expression. Also provided are methods for reducing cellular proliferation and for treating diseases associated with abnormal cellular proliferation.

Abstract: Described herein is the discovery that miR-21 targets and down-regulates the core mismatch repair (MMR) recognition protein complex hMSH2 and hMSH6. Anti-sense miR-21 is therefore proven as therapeutic herein. Therefore, compositions, kits, therapies and other methods, including methods of treatment/amelioration of symptoms, are disclosed herein.