Abstract: Therapeutic uses P2X7 inhibition and inhibition of IRAK1 and/or IRAK4, methods protecting a cell, and screening methods for identifying inhibitors are described herein.

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 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 provides compositions comprising interfering RNA (e.g., siRNA, aiRNA, miRNA) that target polo-like kinase 1 (PLK-1) expression and methods of using such compositions to silence PLK-1 expression. More particularly, the present invention provides unmodified and chemically modified interfering RNA molecules which silence PLK-1 expression and methods of use thereof. The present invention also provides serum-stable nucleic acid-lipid particles (e.g., SNALP) comprising an interfering RNA molecule described herein, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing PLK-1 gene expression by administering an interfering RNA molecule described herein to a mammalian subject. The present invention additionally provides methods of identifying and/or modifying PLK-1 interfering RNA having immunostimulatory properties.

Abstract: Disclosed are dsRNA constructs and methods to control insects via double stranded RNA interference of insect PBAN receptor genes.

Abstract: The present invention provides autonomous replication sequences (ARSs) isolated from Nannochloropsis that support the replication of episomal DNA molecules (EDMs) in eukaryotic cells. The ARSs and EDMs provided herein can be used for expressing genes in organisms including algae and heterokonts.

Abstract: The invention provides methods and compositions for the expression of small RNA molecules within a cell using a lentiviral vector. The methods can be used to express doubles stranded RNA complexes. Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell, which are capable of down regulating the expression of a target gene through RNA interference. A variety of cells can be treated according to the methods of the invention including embryos, embryogenic stem cells, allowing for the generation of transgenic animals or animals constituted partly by the transduced cells that have a specific gene or a group of genes down regulated.

Abstract: Methods of treating, reducing the risk of developing, or delaying the onset of an inflammatory disease are disclosed. The methods involved providing a subject with or at risk of developing an inflammatory disease and administering to the subject an effective amount of a first therapeutic composition comprising miR-124. Further provided are methods of diagnosing a subject with or at risk of developing an inflammatory disease.

Abstract: The invention encompasses methods and kits used in the detection of invasive glioblastoma based upon the expression of NHERF-1. The methods and kits also allow prediction of disease outcome as well as therapeutic outcome.

Abstract: The present invention relates to a recombinant protein for siRNA delivery, which allows the efficient intracellular and in vivo delivery of siRNA. More particularly, the present invention relates to a recombinant protein that allows a siRNA binding protein to be located in the interior cavity of a capsid protein of HBV (Hepatitis B virus), in which siRNAs of interest bind to the siRNA binding protein to be encapsulated within the capsid shell, thereby providing stability against the external attack such as nucleases and achieving the efficient intracellular and in vivo delivery of siRNA by its release into the cytosolic space after cell uptake.

Abstract: This invention provides a method for reducing hypertropic scarring resulting from dermal wound healing in a subject in need which comprises administering to the subject an antisense oligonucleotide which inhibits expression of connective tissue growth factor (CTGF) in an amount effective to inhibit expression of CTGF and thereby reduce hypertrophic scarring.

Abstract: The present invention relates to methods and means for making Vitamin K-dependent protein compositions which are devoid or substantially devoid of protein contaminants. In particular, methods and means useful for the reduction or elimination of protein contaminants also being Vitamin K-dependent proteins are described.

Abstract: In certain embodiments, the invention provides methods for treating cancer, comprising: (a) obtaining a specimen of cancer tissue and normal tissue from a patient; (b) extracting total protein and RNA from the cancer tissue and normal tissue; (c) obtaining a protein expression profile of the cancer tissue and normal tissue; (d) identifying over-expressed proteins in the cancer tissue; (e) comparing the protein expression profile to a gene expression profile; (f) identifying at least one prioritized protein target by assessing connectivity of each said over-expressed protein to other cancer-related or stimulatory proteins; (g) designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding the prioritized target protein; (h): designing a first RNA interference expression cassette to modulate the expression of at least one gene encoding a protein of higher priority in the signaling pathway in which the first protein is a component; (i) incorporating the first cass

Abstract: Described herein are compositions and methods for the inhibition of miR-21 activity. The compositions have certain nucleoside modification patterns that yield potent inhibitors of miR-21 activity. The compositions may be used to inhibit miR-21, and also to treat diseases associated with abnormal expression of miR-21, such as fibrosis and cancer.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a G-alpha q subunit (GNAQ) of a heterotrimeric G gene, and methods of using the dsRNA to inhibit expression of GNAQ.

Abstract: Recombinant proteins for siRNA delivery and a composition including same. These recombinant proteins include a p19 RNA binding protein and a target oriented peptide and can secure the stability of siRNAs from external attacks such as various degradation enzymes, have selective binding affinity to cancer cells by virtue of target-oriented peptides having various cancer cells as their target, and silence target genes by effectively delivering the siRNAs to cells and biological tissues by the release of the siRNAs to the cytoplasms after the cell penetration thereof. Therefore, they are expected to be effectively employed as siRNA delivery vehicles for siRNA therapeutic agents, cell-based drug screening compositions and research.

Abstract: Methods and means are provided for producing chimeric nucleic acid constructs capable of producing dsRNA for silencing target nucleic acid sequences of interest using recombinational cloning.

Abstract: An object of the present invention is to provide an RNAi control system using an RNA-protein interaction motif. The present invention provides an shRNA comprising: a guide strand having a sequence complementary to a target sequence; a passenger strand which forms a duplex with the guide strand; and a linker strand which links the guide strand and the passenger strand, wherein the linker strand comprises an RNP-derived protein-binding motif sequence. The present invention also provides an RNAi control system comprising: the shRNA; and an RNP-derived protein which specifically binds to a protein-binding motif sequence in the shRNA.

Abstract: 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.

Abstract: Methods of treating a wound in a subject are provided comprising administering to the subject an amount of an inhibitor of Fidgetin-like 2. Compositions and pharmaceutical compositions comprising an amount of an inhibitor of Fidgetin-like 2 are also provided. Methods are also provided for identifying an inhibitor of Fidgetin-like 2.

Abstract: A method of treating a disease associated with a cell population which proliferates abnormally in a subject is disclosed. The method comprises administering to the subject a therapeutically effective amount of at least one modulator capable of modulating in the cell population a level and/or activity of a polypeptide having an amino acid sequence at least 60 percent similar to SEQ ID NO: 5, as determined using the Standard protein-protein BLAST [blastp] software of the NCBI.

Abstract: Agents that reduce the amount of IGFBP-2 and/or IGFBP-5 and that are known to be useful in the treatment of cancer result in increased expression of the protein clusterin. Since clusterin can provide protection against apoptosis, this secondary effect detracts from the efficacy of the therapeutic agent. In overcoming this, the present invention provides a combination of therapeutic agents that is useful in the treatment of cancer. The combination includes an agent that reduces the amount of IGFBP-2 and/or IGFBP-5 and that stimulates expression of clusterin as a secondary effect, and an oligonucleotide that is effective to reduce the amount of clusterin in cancer cells. In some embodiments of the invention, the agent that reduces IGFBP-2 and/or IGFBP-5 is a bispecific antisense species. The oligonucleotide may be an antisense oligonucleotide or an RNAi oligonucleotide.

Abstract: Provided are isolated genomic polynucleotide fragments that encode human SNARE YKT6, human glucokinase, human adipocyte enhancer binding protein (AEBP1) and DNA directed 50 kD regulatory subunit (POLD2), vectors and hosts containing these fragments and fragments hybridizing to noncoding regions as well as antisense oligonucleotides to these fragments. The invention is further directed to methods of using these fragments to obtain SNARE YKT6, human glucokinase, AEBP1 protein and POLD2 and to diagnose, treat, prevent and/or ameliorate a pathological disorder.

Abstract: Gene expression can be selectively modulated by contacting a cell with an oligomer that targets a gene region downstream of a ?3-UTR, thereby increasing or decreasing the expression of the target gene.

Abstract: The present invention relates to certain novel shRNA molecules and methods of use thereof. According to certain embodiments of the present invention, methods for reducing the expression level of a target gene are provided. Such methods generally comprise providing a cell with one or more precursor nucleic acid sequences that encode two or more RNA molecules. A first RNA molecule comprises a double stranded sequence, which includes a guide strand sequence that is complementary to a portion of an mRNA transcript encoded by the target gene. In addition, a second RNA molecule comprises a second double stranded sequence, which includes a second guide strand sequence that is partially complementary to a portion of the mRNA transcript encoded by the target gene. Preferably, the second guide strand sequence comprises one or more bases that are mismatched with a nucleic acid sequence of the mRNA transcript encoded by the target gene.

Abstract: The present invention features methods for decreasing the size and density of amyloid plaques, decreasing cognitive decline associated with amyloid pathology, and treating Alzheimer's disease by selectively inhibiting the activity of Acyl-CoA:Cholesterol Acyltransferase 1, but not Acyl-CoA:Cholesterol Acyltransferase 2.

Abstract: Provided are isolated genomic polynucleotide fragments that encode human SNARE YKT6, human glucokinase, human adipocyte enhancer binding protein (AEBP1) and DNA directed 50 kD regulatory subunit (POLD2), vectors and hosts containing these fragments and fragments hybridizing to noncoding regions as well as antisense oligonucleotides to these fragments. The invention is further directed to methods of using these fragments to obtain SNARE YKT6, human glucokinase, AEBP1 protein and POLD2 and to diagnose, treat, prevent and/or ameliorate a pathological disorder.

Abstract: The present invention aims to provide a gene delivery system with higher safety and higher sustainability, which is effective for the treatment of ischemic diseases and the like, and the like. The present invention provides a pharmaceutical composition containing, as an active ingredient, a polyanionic substance that suppresses expression of PHD2, and containing a polyion complex of the polyanionic substance and a polycation chargeable polymer.

Abstract: Provided is a novel nucleic acid molecule that is a single-stranded nucleic acid molecule including an expression inhibitory sequence that inhibits expression of a target gene. The single-stranded nucleic acid molecule includes, in sequence from the 5? side to the 3? side: a 5? side region (Xc); an inner region (Z); and a 3? side region (Yc). The inner region (Z) is composed of an inner 5? side region (X) and an inner 3? side region (Y) that are linked to each other. The 5? side region (Xc) is complementary to the inner 5? side region (X). The 3? side region (Yc) is complementary to the inner 3? side region (Y). At least one of the inner region (Z), the 5? side region (Xc), and the 3? side region (Yc) includes the expression inhibitory sequence.

Abstract: The invention provides a group of nucleic acid fragments, shown in the sequence listing, for prevention of HIV infection or AIDS and the usage thereof. In the invention, a series of RNA fragments, which are highly homogenous to all the published HIV gene sequences, were obtained by homology compare. The double-stranded RNA (dsRNA) derived from these fragments can effectively inhibit the expression of the HIV genes. The RNA transcribed by plasmid, also can suppress the expression of the HIV in the cell. After the adenovirus or associated virus which carry DNA corresponding above RNA infect the cell, the transcription dsRNA can inhibit the expression of the HIV genes.

Abstract: A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. Therefore the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2+/? mice was studied. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation, and inhibited tumor cell invasion, intravasation and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent phenotype of a filopodia-lacking “phalanx” cell type. Without being bound to a particular mechanism, this transition could at least in part be explained by upregulation of (soluble) VEGFR-1 and VE-cadherin.

Abstract: The present invention relates to certain novel shRNA molecules and methods of use thereof. According to certain embodiments of the present invention, methods for reducing the expression level of a target gene are provided. Such methods generally comprise providing a cell with one or more precursor nucleic acid sequences that encode two or more RNA molecules. A first RNA molecule comprises a double stranded sequence, which includes a guide strand sequence that is complementary to a portion of an mRNA transcript encoded by the target gene. In addition, a second RNA molecule comprises a second double stranded sequence, which includes a second guide strand sequence that is partially complementary to a portion of the mRNA transcript encoded by the target gene. Preferably, the second guide strand sequence comprises one or more bases that are mismatched with a nucleic acid sequence of the mRNA transcript encoded by the target gene.

Abstract: The invention provides short interfering nucleic acids, either single-stranded or double-stranded, that cause RNAi-induced degradation of mRNA from the Nav1.8 sodium channel gene; to pharmaceutical compositions comprising such short interfering nucleic acids; recombinant vectors comprising such short interfering nucleic acids; a method for inhibiting translation of an mRNA; a method for inhibiting expression of a polypeptide; a method for blocking the membrane potential in a cell; a method for blocking the sodium current in a cell; and a method for inhibiting chronic pain.

Abstract: The present invention relates to the identification of miRNAs that are involved in the process of neuromuscular synaptic maintenance and regeneration following injury or disease. Modulation of these miRNAs is proposed as treatment for spinal cord injury and neurodegenerative disease.

Abstract: The present disclosure describes the broadly active chelation of diverse divalent 2+ metal cations by any oligonucleotide (ON), regardless of size or modification. This chelation effect is specific to cations which are divalent (or of higher valency) and results in the formation of oligonucleotide chelate complexes which do not behave like salts. It is described herein a novel composition of an ON chelate complex prepared using any ON and a divalent metal cation and methods for the suppression of anti-coagulation and or subcutaneous injection site reactions and or improved tolerability with oligonucleotides by the use of ON chelate complexes during oligonucleotide administration.

Abstract: Provided is a novel nucleic acid molecule that can be produced easily and efficiently and can inhibit the expression of a gene. The nucleic acid molecule is a single-stranded nucleic acid molecule including an expression inhibitory sequence that inhibits expression of a target gene. The single-stranded nucleic acid molecule includes: a region (X); a linker region (Lx); and a region (Xc). The linker region (Lx) is linked between the regions (Xc) and (Xc). The region (Xc) is complementary to the region (X). At least one of the regions (X) and (Xc) includes the expression inhibitory sequence. The linker region (Lx) has a non-nucleotide structure including at least one of a pyrrolidine skeleton and a piperidine skeleton. According to this single-stranded nucleic acid molecule, it is possible to inhibit the expression of the target gene.

Abstract: The invention provides siRNA compositions that interfere with viral replication in respiratory viral infections, including respiratory syncytial virus and avian influenza A, including the H5N1 strain. The invention further provides uses of the siRNA compositions to inhibit expression of viral genes in respiratory virus-infected cells, and to uses in the treatment of respiratory virus infections in a subject. Generally the invention provides polynucleotide that includes a first nucleotide sequence of 15 to 30 bases that targets the genome of a respiratory syncytial virus or an influenza A virus, a complement thereof, a double stranded polynucleotide or a hairpin polynucleotide. Additionally the invention provides vectors, cells and pharmaceutical compositions containing siRNA sequences.

Abstract: The present invention relates to the discovery of an effective treatment for a variety of gain-of-function diseases, in particular, Huntington's disease (HD). The present invention utilizes RNA Interference technology (RNAi) against polymorphic regions in the genes encoding various gain-of-function mutant proteins resulting in an effective treatment for the gain-of-function disease.

Abstract: Medicament comprising a combination of at least one inhibitor of the effect of a substance negatively effecting an immune response, the substance selected from the group consisting of TGF-? and its receptors, VEGF and its receptors, interleukin 10 (IL-10) and its receptors, PGE2 and its receptors, wherein the inhibitor has a molecular weight of less than 100 kDa and at least one stimulator positively effecting an immune response.

Abstract: The present invention provides a method of detecting adventitious agents in a composition comprising a microorganism by using ribozyme-expressing indicator cells, as well as indicator cells useful in such detection.

Abstract: The present invention provides compositions comprising at least one oligomeric compound comprising an alternating motif and further include a region that is complementary to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.

Abstract: An extensible RNA-based framework for engineering ligand-controlled gene regulatory systems, called ribozyme switches, that exhibit tunable regulation, design modularity, and target specificity is provided. These switch platforms typically contain a sensor domain, comprised of an aptamer sequence, and an actuator domain, comprised of a hammerhead ribozyme sequence. A variety of modes of standardized information transmission between these domains can be employed, and this application demonstrates a mechanism that allows for the reliable and modular assembly of functioning synthetic hammerhead ribozyme switches and regulation of ribozyme activity in response to various effectors. In some embodiments aptamer-regulated cis-acting hammerhead ribozymes are provided.

Abstract: Methods and means are provided for reducing the phenotypic expression of a nucleic acid of interest in eucaryotic cells, particularly in plant cells, by introducing chimeric genes encoding sense and antisense RNA molecules directed towards the target nucleic acid, which are capable of forming a double stranded RNA region by base-pairing between the regions with sense and antisense nucleotide sequence or by introducing the RNA molecules themselves. Preferably, the RNA molecules comprises simultaneously both sense and antisense nucleotide sequence.

Abstract: Conserved consensus sequences from known hepatitis B virus strains and known hepatitis C virus strains, which are useful in inhibiting the expression of the viruses in mammalian cells, are provided. These sequences are useful to silence the genes of HBV and HCV, thereby providing therapeutic utility against HBV and HCV viral infection in humans.

Abstract: Disclosed is a dsRNA construct that relates to a method to control Formicidae (ants) via double-stranded RNA interference of the PBAN/Pyrokinin gene.

Abstract: Provided is a method of treating a patient having an inflammatory disease by using a compound which inhibits the complex I-mediated ROS production, a medicament containing such compound and methods for screening for such compounds.

Abstract: Methods and agents for suppressing expression of a mutant allele of a gene and providing a replacement nucleic acid are provided. The methods of the invention provide suppression effectors such as, for example, antisense nucleic acids, ribozymes, or RNAi, that bind to the gene or its RNA. The invention further provides for the introduction of a replacement nucleic acid with modified sequences such that the replacement nucleic acid is protected from suppression by the suppression effector. The replacement nucleic acid is modified at degenerate wobble positions in the target region of the suppression effector and thereby is not suppressed by the suppression effector. In addition, by altering wobble positions, the replacement nucleic acid can still encode a wild type gene product. The invention has the advantage that the same suppression strategy could be used to suppress, in principle, many mutations in a gene.

Abstract: The present invention relates to a double-stranded ribonucleic acid (dsRNA) having a nucleotide sequence which is substantially identical to at least a part of a target gene and which is no more than 49, preferably less than 25, nucleotides in length, and which comprises a complementary (antisense) RNA strand having a 1 to 4 nucleotide overhang at the 3?-end and a blunt 5?-end. The invention further relates to a pharmaceutical composition comprising the dsRNA and a pharmaceutically acceptable carrier. The pharmaceutical compositions are useful for inhibiting the expression of a target gene, as well as for treating diseases caused by expression of the target gene, at low dosages (i.e., less than 5 milligrams, preferably less than 25 micrograms, per kg body weight per day). The invention also relates to methods for inhibiting the expression of a target gene, as well as methods for treating diseases caused by the expression of the gene.

Abstract: Agents that reduce the amount of IGFBP-2 and/or IGFBP-5 and that are known to be useful in the treatment of cancer result in increased expression of the protein clusterin. Since clusterin can provide protection against apoptosis, this secondary effect detracts from the efficacy of the therapeutic agent. In overcoming this, the present invention provides a combination of therapeutic agents that is useful in the treatment of cancer. The combination includes an agent that reduces the amount of IGFBP-2 and/or IGFBP-5 and that stimulates expression of clusterin as a secondary effect, and an oligonucleotide that is effective to reduce the amount of clusterin in cancer cells. In some embodiments of the invention, the agent that reduces IGFBP-2 and/or IGFBP-5 is a bispecific antisense species. The oligonucleotide may be an antisense oligonucleotide or an RNAi oligonucleotide.

Abstract: A capture probe suitable for use with a method for isolating miRNAs. A method for isolating an miRNA of interest from a sample comprising the miRNA of interest comprising providing the capture probe. A method for identifying an miRNA of interest.