Abstract: The invention provides interfering RNA molecule-ligand conjugates useful as a delivery system for delivering interfering RNA molecules to a cell in vitro or in vivo. The conjugates comprise a ligand that can bind to a transferrin receptor (TfR). Therapeutic uses for the conjugates are also provided.

Abstract: The present invention is based on the findings that a novel function for miR142-3p in the regulation of Sox2, adenylyl cyclase 9 (AC9), and CD133 expressions, and consequently the overall stemness of recurrent GBM cells as well as CSCs, and that miR142-3p modulated tumor-initiating properties in recurrent GBM. The present invention consequently supports the development of novel miRNA-based strategies for brain tumor treatment.

Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted melittin delivery peptides. Delivery peptides provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery peptides.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a SCAP gene (Human SCAP gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of a SCAP gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by Human SCAP expression and the expression of a SCAP gene using the pharmaceutical composition; and methods for inhibiting the expression of a SCAP gene in a cell.

Abstract: A method of processing a target RNA is provided. In certain embodiments, this method comprises: contacting the products of an RNA ligase-mediated ligation reaction with an CAS6 protein, wherein: (i) the RNA ligase-mediated ligation reaction comprises: a target RNA, an RNA ligase, and first and second adaptors that can ligate together to produce an adaptor dimer that contains a CRISPR stem loop; and (ii) the CAS6 protein recognizes the CRISPR stem loop; thereby preventing the adaptor dimer from being reverse transcribed.

Abstract: The present invention relates to pharmaceutical compositions useful for topical, non-invasive delivery of an oligonucleotide to the ear and to methods for the treatment of an ear disorder, including hearing loss arising from chemical-induced ototoxicity, acoustic trauma and presbycusis; and microbial infections. The method comprises topically administering to the ear of a subject in need thereof a pharmaceutical composition comprising an inhibitory oligonucleotide, a permeability enhancer and a pharmaceutically acceptable carrier, wherein the oligonucleotide reduces or inhibits expression of a gene associated with the ear disorder in the subject.

Abstract: The invention is to methods of gene silencing in arthropods using dsRNA. The method is include contacting the arthropod with, and/or directly feeding the arthropod, the dsRNA to the arthropods to deliver the dsRNA to arthropod tissues. It is envisaged that the methods of the invention will have use in determining the biological function of genes in arthropods. Methods of pest control of arthropods, and of protecting arthropods against parasites and predators are provided. Transgenic arthropods expressing dsRNA molecules are also provided by the present invention.

Abstract: The present invention provides double-stranded RNA molecules that mediate RNA interference in target cells, preferably hepatic cells. The invention also provides double-stranded RNA (dsRNA) molecules that are modified to be resistant to nuclease degradation, which inactivates a virus, and more specifically, hepatitis C virus (HCV). The invention also provides a method of using these modified RNA molecules to inactivate virus in mammalian cells and a method of making modified small interfering RNAs (siRNAs) using human Dicer. The invention provides modified RNA molecules that are modified to include a dsRNA or siRNA wherein one or more of the pyrimidines in the RNA molecule are modified to include 2?-Fluorine. The invention also provides dsRNA or siRNA in which all pyrimidines are modified to include a 2?-Fluorine. The invention provides that the 2?-Fluorine dsRNA or siRNA molecule is further modified to include a two base deoxynucleotide “TT” sequence at the 3? end of the molecule.

Abstract: Therapeutic agents which target heat shock protein (hsp) 27 in vivo are used to provide treatment to individuals, particularly human individuals, suffering from prostate cancer and other cancers that overexpress hsp27. A therapeutic agent, for example an antisense oligonucleotide or RNAi nucleotide inhibitor with sequence specificity for hsp27 mRNA, for example human hsp27 mRNA, is administered to an individual suffering from prostate cancer or some other cancer expressing elevated levels of hsp 27 in a therapeutically effective amount. The therapeutic agent is suitably formulated into a pharmaceutical composition which includes a pharmaceutically acceptable carrier, and packaged in dosage unit form. A preferred dosage unit form is an injectable dosage unit form.

Abstract: The present disclosure relates to RNAi agents useful in methods of treating Beta-ENaC-related diseases such as cystic fibrosis, pseudohypoaldosteronism type 1 (PHA1), Liddle's syndrome, hypertension, alkalosis, hypokalemia, and obesity-associated hypertension, using a therapeutically effective amount of a RNAi agent to Beta-ENaC.

Abstract: The present invention relates to compositions comprising a therapeutically effective amount of miRNAs, their use for the treatment of medical conditions benefiting from being treated with these compositions, as well as methods for the preparation of compositions comprising miRNAs.

Abstract: The present disclosure provides meroduplex (nicked or gapped) ribonucleic acid molecules (mdRNA) that decreases or silences target gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a target gene RNA. In addition, the meroduplex may have one or more modifications or substitutions, such as nucleotide base, sugar, terminal cap structure, internucleotide linkage, or any combination of such modifications. Also provided are methods of decreasing expression of a target gene in a cell or in a subject to treat a disease related to altered expression of a target gene.

Abstract: The present invention relates to the E2EPF UCP-VHL interaction and the uses thereof, more precisely a method for increasing or reducing VHL activity or level by regulating UCP activity or level to inhibit cancer cell proliferation or metastasis or to increase angiogenesis. The inhibition of UCP activity is accomplished by any UCP activity inhibitor selected from a group consisting of a small interfering RNA (RNAi), an antisense oligonucleotide, and a polynucleotide complementarily binding to mRNA of UCP, a peptide, a peptide mimetics and an antibody, and a low molecular compound. In the meantime, the increase of angiogenesis is accomplished by the following mechanism; UCP over-expression is induced by a gene carrier and thus endogenous VHL is reduced, leading to the stabilization of HIF-1? which enhances VEGF activation based on the HIF-1? stabilization.

Abstract: Intact, bacterially-derived minicells can safely introduce therapeutically effective amount 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: The present invention relates, in general, to glycoprotein VI (GPVI) and, in particular, to aptamers to GPVI and to compositions comprising same. The invention also relates to methods of inhibiting platelet aggregation using an aptamer that binds to and inhibits the activity of GPVI. The invention further relates to antidotes to GPVI aptamers and to methods of using such antidotes to reverse aptamer-induced platelet inhibition. The invention also relates to aptamers that bind to and enhance the activity of GPVI.

Abstract: The present invention relates to the E2EPF UCP-VHL interaction and the uses thereof, more precisely a method for increasing or reducing VHL activity or level by regulating UCP activity or level to inhibit cancer cell proliferation or metastasis or to increase angiogenesis. The inhibition of UCP activity is accomplished by any UCP activity inhibitor selected from a group consisting of a small interfering RNA (RNAi), an antisense oligonucleotide, and a polynucleotide complementarily binding to mRNA of UCP, a peptide, a peptide mimetics and an antibody, and a low molecular compound. In the meantime, the increase of angiogenesis is accomplished by the following mechanism; UCP over-expression is induced by a gene carrier and thus endogenous VHL is reduced, leading to the stabilization of HIF-1? which enhances VEGF activation based on the HIF-1? stabilization.

Abstract: Methods, compositions and kits are provided for increasing the expression of a gene product in a cell by contacting the cell with a modified small activating RNA (saRNA) molecule, which provides for an increase in gene expression that is improved over the increase in expression provided by traditional saRNAs. These methods and compositions find use in any application in which an increase in gene expression in a cell is desired.

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: 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 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.