Abstract: The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.

Abstract: The invention relates to the cancer antigen PRAME (PReferentially expressed Antigen in MElanoma) and its use in a method of treatment of a tumour which comprises administering to a subject in need of treatment an effective amount of an inhibitor of PRAME, in combination with a second agent selected from the group of an inhibitor of HDAC (an HDACi) and a retinoid.

Abstract: Disclosed are bispecific aptamers binding with high specifity to a tumour specific antigen (TSA) and a effector cell specific antigen (ESA) for treatment of cancer.

Abstract: Provided herein are methods of producing enhanced placental stem cells by modulatory RNA molecules. Also provided herein are methods of using enhanced placental stem cells, for example, to treat individuals having a disease, disorder or condition caused by, or relating to, an unwanted or harmful immune response. Further provided herein are compositions comprising said enhanced placental stem cells.

Abstract: The present invention is related to hybrid conjugates formed by covalently bonding siRNA (small interfering RNA) molecules to hydrophilic polymers for improving stability of the siRNA molecules effective for delivering the siRNA in vivo, and polyelectrolyte complex micelles formed by ionic interactions between the conjugates and multifunctional cationic compounds. The siRNA-hydrophilic polymer conjugates and polyelectrolyte complex micelles derived therefrom can be used for improving stability of the siRNA molecules in vivo. Consequently, the delivery of siRNA molecules for therapeutic applications into cells can be facilitated, and the siRNA is still active even though a small dose of the siRNA is used.

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 and compositions for genetic alteration of cells are provided.

Abstract: The present invention concerns Zdhhc2, a new target involved in adipogenesis modulation. Using a siRNA approach, the inventors demonstrated that decrease in Zdhhc2 activity in adipose tissue induces a decrease in adipogenesis. Thus, the present invention relates to modulators of Zdhhc2 activity as well as screening test for identification of modulators of the activity of this target, and their use, especially in pharmaceutical composition, to modulate adipogenesis and thus treat obesity and related disorders.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Pancreatic Developmental gene, in particular, by targeting natural antisense polynucleotides of a Pancreatic Developmental gene. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Pancreatic Developmental genes.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing KRAS target RNA and protein levels via use of Dicer substrate siRNA (DsiRNA) agents possessing asymmetric end structures.

Abstract: An object of the present invention is to provide DNA which regulates the expression of miR-140, a reporter vector which contains the DNA, cells and animals into which the reporter vector is introduced and a screening system for drugs which control the expression of miR-140 and is also to contribute in the development of new therapeutic agents for cartilage diseases such as osteoarthritis and intervertebral disk degeneration using the screening system. The DNA sequence according to the present invention is able to express any gene in a site where miR-140 is expressed and, in addition, it is also able to be utilized for screening a drug which regulates the expression of miR-140. Moreover, the drug that is selected by the screening system of the present invention is expected as a therapeutic agent for cartilage diseases accompanied by abnormality of cartilage.

Abstract: The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.

Abstract: The present invention relates to the provision of a DNA sequence of the major grass pollen allergen Lol p 4. The invention also encompasses fragments, new combinations of partial sequences and point mutants having a hypoallergenic action. The recombinant DNA molecules and the derived polypeptides, fragments, new combinations of partial sequences and variants can be utilised for the therapy of pollen-allergic diseases. The proteins prepared by recombinant methods can be employed for in vitro and in vivo diagnosis of pollen allergies.

Abstract: Antisense sequences, including duplex RNAi compositions, which possess improved properties over those taught in the prior art are disclosed. The invention provides optimized antisense oligomer compositions and method for making and using the both in in vitro systems and therapeutically. The invention also provides methods of making and using the improved antisense oligomer compositions.

Abstract: The present invention relates to the identification of two microRNAs, miR-499 and miR-208b, that repress fast skeletal muscle contractile protein genes. Expression of miR-499 and/or miR-208b can be used to repress fast fiber genes and activate slow fiber genes in the treatment of musculoskeletal disorders. Inhibition of miR-499 and/or miR-208b is proposed as a treatment for cardiac hypertrophy, myocardial infarction, and/or heart failure. Pharmaceutical compositions comprising antagonists and agonists of miR-499 and miR-208b function are also disclosed.

Abstract: The present invention provides isolated polynucleotide sequences encoding ?-mannosidase. The present invention further provides DNA constructs comprising the polynucleotide sequence coding for ?-mannosidase in sense or anti-sense orientation, RNAi constructs, recombinant vectors comprising the constructs, and host cells comprising the recombinant vector. The present invention further provides transgenic plants, plant cells, transgenic progeny and seeds expressing the polynucleotide with reduced ?-mannosidase protein accumulation, having enhanced fruit shelf life.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Pyrroline-5-carboxylate reductase 1 (PYCR1), in particular, by targeting natural antisense polynucleotides of Pyrroline-5-carboxylate reductase 1 (PYCR1). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of PYCR1.

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: Innovative graft polymers designed for the efficient delivery of antisense molecules into biological cells and for maintaining the biological activity of these molecules while in serum and other aqueous environments are provided. Such polymers may comprise an anionic graft polymer comprising an anionic polymer backbone with pendant carboxylic acid groups and pendant chains comprising amphipathic or hydrophilic polymers covalently bonded to a portion of said pendant carboxylic acid groups. Antisense molecule delivery vectors comprising such polymers in combination with cationic agents for delivery of antisense molecules are also disclosed.

Abstract: Disclosed are oligomeric compounds which are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. The hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

Abstract: Methods and compositions are provided which employ a silencing element that, when ingested by a pest, such as a Pentatomidae plant pest or a N. viridula, Acrosternum hilare, Piezodorus guildini, and/or Halymorpha halys plant pest, decrease the expression of a target sequence in the pest. In specific embodiments, the decrease in expression of the target sequence controls the pest and thereby the methods and compositions are capable of limiting damage to a plant. The present invention provides various target polynucleotides set forth in any one of SEQ ID NOS: 1-292 or 302-304 or active variants and fragments thereof, wherein a decrease in expression of one or more the sequences in the target pest controls the pest (i.e., has insecticidal activity). Further provided are silencing elements which when ingested by the pest decrease the level of the target polypeptide and thereby control the pest. In specific embodiment, the pest is Pentatomidae.

Abstract: Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

Abstract: Provided are methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization. Administration of stimulators of the TLR3 and TLR7 receptors, Trif or of IL-10 and IL-12 inhibits ocular angiogenesis. Furthermore, all siRNAs (both targeted and non-targeted) can inhibit ocular angiogenesis.

Abstract: Provided herein are methods directed to modulating the pro-oncogenic effects of noncoding RNAs (ncRNAs) through their interactions with specificity protein transcription factors (SpTFs). In one aspect, the disclosure provides a method of inhibiting growth of a cell, such as a transformed or cancer cell, characterized by overexpression of at least one specificity protein (Sp)-regulated ncRNA and expression of at least one Sp transcription factor (SpTF), the method comprising contacting the cell with an effective amount of an SpTF agent. In some embodiments, the ncRNA is a long noncoding RNA (lncRNA). In some embodiments, the ncRNA is a microRNA (miR). Also provided are methods of treating a cell proliferative disease, predicting the response of a subject to SpTF agent-based treatment, and monitoring the efficacy of a SpTF agent-based treatment in a subject.

Abstract: The present invention provides devices, small interfering RNAs, and methods for treating a neurodegenerative disorder comprising the steps of surgically implanting a catheter so that a discharge portion of the catheter lies adjacent to a predetermined infusion site in a brain, and discharging through the discharge portion of the catheter a predetermined dosage of at least one substance capable of inhibiting production of at least one neurodegenerative protein. The present invention also provides valuable small interfering RNA vectors, systems, and methods for treating Huntington's disease in vivo without impairment of cell endoplasmic reticulum, spontaneous motor activity, or locomotor activity of a patient.

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: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Reprogramming factor, in particular, by targeting natural antisense polynucleotides of a Reprogramming factor. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Reprogramming factors.

Abstract: The present inventors focused on siE sequences that have been thought to show RNAi activity against HCV viral RNAs, and mainly selected the D5-50 and D5-197 regions present within the IRES region, and carried on the analysis. As a result, the present inventors successfully identified siRNA sequences that exhibit a more effective RNAi activity against hepatitis C virus RNAs. Furthermore, the siRNAs were demonstrated to have a significant inhibitory effect on HCV propagation in an in vivo system.

Abstract: Short interfering ribonucleic acid (siRNA) for oral administration, said siRNA comprising two separate RNA strands that are complementary to each other over at least 15 nucleotides, wherein each strand is 49 nucleotides or less, and wherein at least one of which strands contains at least one chemical modification.

Abstract: Intact, bacterially-derived minicells can safely introduce therapeutically effective amounts of plasmid-free functional nucleic acid to target mammalian cells. To this end, functional nucleic acid can be packaged into intact minicells directly, without resort to expression constructs, the expression machinery of the host cell, harsh chemicals or electroporation.

Abstract: This invention provides treatment compositions as well as systems and methods of determining and administering an effective amount of treatment for a neurological disorder. The treatment composition can contain a labeled interfering RNA (iRNA) agent capable of decreasing expression of a target RNA associated with the neurological disorder. The methods of the invention include determining an effective amount of a therapeutic composition by introducing a solution containing a tracer into the brain of a mammal. The tracing solution is monitored until a target volume of distribution at steady state distribution is substantially achieved, and the rate of delivery of the therapeutic composition is determined. The therapeutic composition can then be administered at the rate determined by use of the tracing solution.

Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.

Abstract: The present invention relates to compositions and methods for diagnosing, preventing and treating intracranial aneurysm.

Abstract: The current invention provides an improved oligonucleotide and its use for treating, ameliorating, preventing and/or delaying DMD or BMD.

Abstract: The present disclosure relates to Birt-Hogg-Dubé syndrome, nucleic acids encoding the BHD gene, and methods of using the nucleic acids and proteins encoded thereby. In particular, the present disclosure relates to methods of diagnosing BHD disease and related conditions, such as spontaneous pneumothorax and kidney cancer, and methods of treating BHD skin lesions.

Abstract: The present invention relates to the specific inhibition of gene expression in mammals by bringing the target gene into contact with double stranded RNA (dsRNA).

Abstract: A non-human transgenic animal having a polynucleotide encoding a PTN polypeptide, which polynucleotide is operably linked to a promoter, wherein said transgenic animal has greater than wild-type expression of the PTN polypeptide in at least one brain region, as well as related vectors, methods of producing transgenic animals, in vitro and in vivo screening methods for potential therapeutic agents, and methods for treating and diagnosing neuropsychiatric illnesses, particularly anxiety and depression, are disclosed.

Abstract: Certain disclosed oligomers induce exon skipping during processing of myostatin pre-mRNA. The oligomers may be in a vector or encoded by the vector. The vector is used for inducing exon skipping during processing of myostatin pre-mRNA. A therapeutically effective amount of the oligomer may be administered to a subject patient such that exon skipping during processing of myostatin pre-mRNA is induced. The administration to a subject may be used in order to increase or maintain muscle mass, or slowing degeneration of muscle mass in the subject. The administration to a subject may ameliorate muscle wasting conditions, such as muscular dystrophy.

Abstract: The present invention relates to the use of the miRNA expression profile, particularly of miR-199a-5p, and the target genes regulated thereby for the diagnosis, prognosis and use of miR-199a-5p inhibitors for treating fibroproliferative disorders.

Abstract: The invention relates to an in vitro method for identifying the sequence of one or more poly(A)+RNA molecules that physically interacts with protein. The present invention provides a method to define the protein-bound transcriptome under any given cellular condition, such as a disease condition or after treatment with any given substance, drug, or other cellular perturbation. The invention also relates to a method for identification of a drug target and a method for the identification of one or more biomarkers, preferably for identification of a panel of biomarkers, for any given medical condition, comprising the method of the invention.

Abstract: The disclosure relates to an RNA interference (RNAi) agent and the use of that RNAi agent to treat chronic pain in individuals, as well as pharmaceutical compositions containing the RNAi agents of the invention. The DNA-directed RNA interference (ddRNAi) agent for inhibiting expression of one or more target sequences in a pain associated gene comprises, one or more effector sequence sequences and effector complement sequences of at least 17 nucleotides in length, wherein the effector sequence is substantially complementary to the predicted transcript of a target sequence within a pain associated gene.

Abstract: The present invention aims to develop and provide a method for identifying a disease associated with the abundance of TDP-43 in cells and a method for producing a TDP-43 binding inhibitor. By measuring the abundance of a measurement substance, the amount of binding between a measurement substance and TDP-43, etc. in cells obtained from a subject, it is identified whether or not the subject is suffering from a disease associated with the abundance of TDP-43 in cells. Also, a drug which can significantly reduce the binding between a measurement substance and TDP-43 is produced by adding a drug candidate substance.

Abstract: Methods for determining the presence of cancer stem cells by detecting GD2 expression. Also provided are methods for reducing proliferation of cancer stem cells by contacting the cells with a GD2 targeting agent, such as an anti-GD2 antibody or a GD3 synthase inhibitor. GD3 synthase inhibitor compounds are also provided.

Abstract: By a QTL analysis and so forth using 4-HPPD inhibitor-susceptible rice and 4-HPPD inhibitor-resistant rice, a hypothetical gene (HIS1 gene) of an iron/ascorbate-dependent oxidoreductase gene located on a short arm of chromosome 2 of rice has been identified as a 4-HPPD inhibitor-resistance gene. Further, it has also been revealed that a homologous gene (HSL1 gene) of the HIS1 gene is located on chromosome 6 of rice. Furthermore, it has been found out that utilizations of these genes make it possible to efficiently produce a plant having increased resistance or susceptibility to a 4-HPPD inhibitor and to efficiently determine whether a plant has resistance or susceptibility to a 4-HPPD inhibitor.

Abstract: Disclosed herein are compounds, compositions and methods for modulating the expression of huntingtin in a cell, tissue or animal. Further provided are methods of slowing or preventing Huntington's Disease (HD) progression using an antisense compound targeted to huntingtin. Additionally provided are methods of delaying or preventing the onset of Huntington's Disease (HD) in an individual susceptible to Huntington's Disease (HD). Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Paraoxonase 1(PON1), in particular, by targeting natural antisense polynucleotides of Paraoxonase 1(PON1). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of PON1.

Abstract: A method of increasing insulin content in a pancreatic beta cell is disclosed. The method comprising expressing in the pancreatic beta cell an exogenous polynucleotide encoding at least one microRNA or a precursor thereof, wherein the microRNA is selected from the group consisting of miR-15, miR-16, miR-24, miR-26, miR-27, miR-29, miR-30, miR-129, miR-141, miR-148, miR-182, miR-200, miR-376 and Let-7, thereby increasing the insulin content in the pancreatic beta cell.

Abstract: The present invention relates to oligonucleotides for modulation of target RNA activity. Thus, the invention provides oligonucleotides that bind to microRNA binding sites of target RNA. The oligonucleotides may activate RNase H or RNAi. In a preferred embodiment, the oligonucleotides prevents a microRNA from binding to its binding site of the target RNA and thereby prevent the microRNA from regulating the target RNA. Such oligonucleotides have uses in research and development of new therapeutics.

Abstract: The present invention relates to a method for treating a brain injury due to a traumatic event, disease or ischemic attack in a mammal subject, wherein the method comprises administering to the mammal subject an effective amount of miR-23a-3p and/or miR-27a-3p mimics to reduce activation of Puma, Noxa and Bax therby causing a subsequent reduction in neuronal apoptosis.

Abstract: The invention provides compositions and methods for reducing expression of a target gene in a cell, involving contacting a cell with an isolated double stranded nucleic acid (dsNA) in an amount effective to reduce expression of a target gene in a cell. The dsNAs of the invention possess a single stranded extension (in most embodiments, the single stranded extension comprises at least one modified nucleotide and/or phosphate back bone modification). Such single stranded extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be effective RNA inhibitory agents compared to corresponding double stranded DsiRNAs.