Abstract: The present invention relates to the regulation of apoptosis and expression of the BH3-only family of genes by miR-29. The invention further relates to the use of miR-29 to protect cells from apoptosis and to treat disorders associated with apoptosis.

Abstract: Embodiments are related to nonviral gene delivery vectors using only FDA-approved components: iopamidol, protamine, and ethiodized oil.

Abstract: The present invention provides agents, compositions, constructs and methods for silencing HCV polynucleotides, as well as methods and compositions for treating or preventing HCV infection in a mammalian cell. In one aspect, the present invention provides an agent or composition comprising at least one double-stranded RNA effector molecule or complex. The double-stranded RNA effector molecule or complex comprises: (1) a sequence of at least 19 nucleotides having at least 90% identity with a nucleotide sequence within HCV Conserved Region 1 (SEQ ID NO: 2), HCV Conserved Region 2 (SEQ ID NO: 3), HCV Conserved Region 5 (SEQ ID NO: 4), (ATR)-1 (SEQ ID NO: 86), ATR-2 (SEQ ID NO: 87), ATR-3 (SEQ ID NO: 88), ATR-4 (SEQ ID NO: 89); and (2) its complementary sequence. In another aspect, the present invention provides a construct suitable for replication in a host cell, and/or suitable for expression of an RNA molecule or complex of the invention in vitro or in vivo.

Abstract: Disclosed herein are compositions and methods for treatment of muscle dysfunction, including diabetes. In addition, the invention relates to therapeutic compositions comprising nucleotides and/or polypeptides of the invention in combination with a pharmaceutically acceptable carrier, wherein the composition facilitates the treatment of skeletal muscle disorders. Moreover, the invention relates to the treatment and/or prevention of pathological conditions associated with altered intracellular Ca2+ regulation and disrupted membrane structure that occurs when the expression levels of MG29 are reduced.

Abstract: Disclosed herein are compositions and methods for treatment of muscle dysfunction (including sarcopenia) and other diseases involving skeletal muscle, including age-related muscle dysfunction. In addition, the invention relates to therapeutic compositions comprising nucleotides and/or polypeptides of the invention in combination with a pharmaceutically acceptable carrier, wherein the composition facilitates the treatment of skeletal muscle disorder, including those related to thr normal aging process. Moreover, the invention relates to the treatment and/or prevention of pathological conditions associated with altered intracellular Ca2+ regulation and disrupted membrane structure that occurs when the expression levels of MG29 are reduced.

Abstract: Parkinson's disease is caused by the preferential loss of substantia nigra dopamine neurons. A Parkin Interacting Substrate, PARIS (ZNF746) is identified. The levels of PARIS are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin. PARIS is a KRAB and zinc finger protein that accumulates in models of parkin inactivation and in human brain Parkinson's disease patients. PARIS represses the expression of the transcriptional co-activator, PGC-1? and the PGC-1? target gene, NRF-1 by binding to insulin response sequences in the PGC-1? promoter. Conditional knockout of parkin in adult animals leads to progressive loss of dopamine (DA) neurons that is PARIS dependent. Overexpression of PARIS causes selective loss of DA neurons in the substantia nigra, which is reversed by either parkin or PGC-1? co-expression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.

Abstract: The present inventors discovered that siRNAs targeting the 17AA site of the WT1 gene not only suppress the expression of the WT1 gene, but also demonstrate remarkable cell growth-suppressing effects and cell death-inducing effects in cancer cell lines.

Abstract: Provided herein are methods and compositions for the treatment of metabolic disorders. Also provided herein are methods and compositions for the reduction of blood glucose level, the reduction of gluceoneogenesis, the improvement of insulin resistance and the reduction of plasma cholesterol level. In certain embodiments, the methods comprise inhibiting the activity of miR-103. In certain embodiments, the methods comprise inhibiting the activity of miR-107. In certain embodiments, the activity of both miR-103 and miR-107 is inhibited. In certain embodiments, such methods comprise administering a compound comprising an oligonucleotide targeted to a microRNA.

Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. The public miRNA database contains 321 human miRNA sequences, 234 of which have been experimentally verified. To explore the possibility that additional miRNAs are present in the human genome, we have developed an experimental approach called miRNA serial analysis of gene expression (miRAGE) and used it to perform the largest experimental analysis of human miRNAs to date. Sequence analysis of 273,966 small RNA tags from human colorectal cells allowed us to identify 200 known mature miRNAs, 133 novel miRNA candidates, and 112 previously uncharacterized miRNA* forms. To aid in the evaluation of candidate miRNAs, we disrupted the Dicer locus in three human colorectal cancer cell lines and examined known and novel miRNAs in these cells. The miRNAs are useful to diagnose and treat cancers.

Abstract: The present invention provides a method of inhibiting cancer cell proliferation by suppressing a function of ZNF143, a cancer cell proliferation inhibitor containing as an active ingredient a substance capable of inhibiting a function of ZNF143, like a ZNF143-specific siRNA, a prophylactic and/or therapeutic drug for cancer, a method of detecting cancer cells, a diagnostic reagent for cancer, a vector and transformant cell incorporating the vector, and a screening method for a substance possessing cancer cell proliferation inhibitory activity with the amount of inhibition of the binding of ZNF143 protein as an index.

Abstract: The present invention relates to oligomer compounds (oligomers), which target PCSK9 mRNA in a cell, leading to reduced expression of PCSK9. Reduction of PCSK9 expression is beneficial for the treatment of certain medical disorders, such as hypercholesterolemia and related disorders.

Abstract: Cdc25A is herein identified as a substrate for ?-TrCP1- or ?-TrCP2-mediated ubiquitination and subsequent degradation via the ubiquitin-proteasome pathway. In particular, it has been found that interfering with ?-TrCP expression or function, or increasing ?-TrCP degradation, leads to accumulation of Cdc25A in a cell. Since degradation of Cdc25A is a key feature of the response to DNA damage, leading to a stall in the cell cycle during which the cell can repair the damage, Cdc25A accumulation can abolish this response, thereby sensitizing the cell to DNA damage. Described herein are assays for identifying ?-TrCP inhibitors, and method of using such inhibitors for modulating Cdc25A degradation, sensitization of tumor cells, and as adjuvants in cancer therapy based on DNA damaging agents.

Abstract: RNA interference using small interfering RNAs which are specific for the vascular endothelial growth factor (VEGF) gene and the VEGF receptor genes Flt-1 and Flk-1/KDR inhibit expression of these genes. Diseases which involve angiogenesis stimulated by overexpression of VEGF, such as diabetic retinopathy, age related macular degeneration and many types of cancer, can be treated by administering the small interfering RNAs.

Abstract: Disclosed herein are compounds and methods for decreasing SMRT and treating metabolic and/or cardiovascular diseases in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to SMRT include obesity, diabetes, dyslipidemia, and hypothyroidism.

Abstract: RNA interference using small interfering RNAs which are specific for the vascular endothelial growth factor (VEGF) gene and the VEGF receptor genes Flt-1 and Flk-1/KDR inhibit expression of these genes. Diseases which involve antiogenesis stimulated by overexpression of VEGF, such as diabetic retinopathy, age related macular degeneration and many types of cancer, can be treated by administering the small interfering RNAs.

Abstract: Methods are provided for modulating RBP4 by administering a RBP4-specific modulator. Also provided are methods for treating cardiovascular and metabolic disorders in a subject or delaying or preventing risk factors thereof through the modulation of RBP4. The present invention is also directed to methods of decreasing lipid levels in a subject or for preventing or delaying the onset of a rise in lipid levels in a subject, comprising administering to said subject a RBP4-specific inhibitor.

Abstract: The invention provides methods of treating certain blood related disorders, in particular, thrombocytopenia and anemia comprising increasing miR-150 expression or inhibiting miR-150 in progenitor cells respectively.

Abstract: Compounds, compositions and methods are provided for modulating the expression of apolipoprotein C-III. The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein C-III. Methods of using these compounds for modulation of apolipoprotein C-III expression and for diagnosis and treatment of disease associated with expression of apolipoprotein C-III are provided.

Abstract: The present invention provides antisense antiviral compounds, compositions, and methods of their use and production, mainly for inhibiting the replication of viruses of the Filoviridae family, including Ebola and Marburg viruses. The compounds, compositions, and methods also relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds include phosphorodiamidate morpholino oligonucleotides (PMOplus) having a nuclease resistant backbone, about 15-40 nucleotide bases, at least two but typically no more than half piperazine-containing intersubunit linkages, and a targeting sequence that is targeted against the AUG start site region of Ebola virus VP35, Ebola virus VP24, Marburg virus VP24, or Marburg virus NP, including combinations and mixtures thereof.

Abstract: The invention encompasses methods of delivering nucleic acids, including dsRNA, to mammalian target cells in vivo via intercellular transfer, wherein the dsRNA is delivered to or expressed in a first cell different from the target cell, wherein the first cell facilitates delivery of the dsRNA to the target cell.