Abstract: Compositions and methods of modulating an immune response by controlling expression levels of microRNAs in dendritic cells are disclosed. In particular, the invention relates to modified dendritic cells and methods of using such dendritic cells in cellular therapy for treating various immune conditions and diseases, including transplant rejection, inflammatory disorders, autoimmune diseases, allergies, infectious diseases, immunodeficiency, and cancer.

Abstract: Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Ago2 because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

Abstract: The present invention relates to a composition for inhibiting growth of cancer stem cells, which includes an EXT1, LDHB, CD109, EFEMP2, RASIP1 or SERPINE1 gene expression inhibitor as an active ingredient, and a method of treating cancer using the same. The composition has targeted therapeutic activities against cancer stem cells important for resistance, metastasis and recurrence of breast cancer, and thus can be useful in fundamentally treating, preventing or alleviating cancer such as breast cancer by directly inhibiting expression of EXT1, LDHB, CD109, EFEMP2, RASIP1 or SERPINE1 which are very important for growth of the cancer stem cells.

Abstract: The invention provides methods for determining the susceptibility of cancer patients to developing adverse reactions if treated with a telomerase inhibitor drug by measurement of telomere length in appropriate cells of the patient prior to initiation of the telomerase inhibitor treatment.

Abstract: The present disclosure provides pharmaceutical compositions and methods useful for modulating angiogenesis and for inhibiting metastasis, tumors, pulmonary alveolar proteinosis, and fibrosis in a mammalian tissue. Pharmaceutical compositions and methods include inhibitors of LOXL2 expression and activity, such as shRNA targeting LOXL2.

Abstract: Cancer treatment methods comprising a step of applying remote conditioning to the cancer subject, for example remote ischemic conditioning via several episodes of short-term limb occlusion. Upregulation and release of remote conditioning substances such as microRNA 144/451 cluster endogenously caused by remote conditioning may be beneficial in reducing the growth and proliferation of malignant cells. Remote conditioning may also be beneficial when combined with chemotherapy or radiation therapy as it may improve survival of healthy surrounding tissues and minimize side effects of these known cancer treatments. Remote conditioning may be non-invasively applied by a medical professional or self-applied by the cancer subject at home using an automatic device. The novel cancer treatment methods may be used for lung cancers, liver cancers, colorectal cancers, digestive cancers and other cancers.

Abstract: Embodiments concern methods and compositions involving miR-124 mimics. In some embodiments, there are double-stranded RNA molecules with modified nucleotides having an active strand with a miR-124 sequence and a complementary passenger strand.

Abstract: Peptides that have been found to facilitate the delivery of siRNA molecules into cells and to function in siRNA mediated silencing of cellular targets are disclosed. Complexes that include one of the peptides and a cargo molecule are disclosed, wherein the peptide and the cargo molecule are coupled non-covalently. Also disclosed are methods of producing and using the peptides/complexes.

Abstract: The present invention is directed to methods and methods for the treatment, inhibition and/or reduction, and detection of metastatic tumors. In some embodiments, the inventive methods include systemic (e.g., intravenous) administration of a chlorotoxin agent that may or may not be labeled. In some embodiments, the inventive methods allow treatment, inhibition and/or reduction, and detection of metastases in the brain. In some embodiments, neovascularization is inhibited and/or newly formed vessels are caused to regress.

Abstract: It is disclosed a method for treating hepatitis B virus infection or hepatitis B virus/hepatitis delta virus co-infection, the method comprising administering to a subject in need of such treatment a first pharmaceutically acceptable agent that comprises at least one phosphorothioated nucleic acid polymer and a second pharmaceutically acceptable agent that comprises at least one nucleoside/nucleotide analog HBV polymerase inhibitor.

Abstract: The present invention provides minimally invasive methods of detecting, diagnosing, and assessing neuronal damage associated with traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE). Specific species of microRNAs (miRNA), small, noncoding RNA molecules that play gene regulatory functions, are correlated with cellular damage and oxidative stress following TBI or CTE, allowing for rapid, minimally-invasive diagnosis and assessment of brain injury. The early identification and longitudinal assessment of neuronal damage in subjects suffering from or at risk of suffering from a TBI (e.g., football players, boxers, military personnel, fall victims) will improve clinical outcomes by guiding critical medical and behavioral decision making.

Abstract: MicroRNAs (miRNAs) are a diverse and abundant class of ˜22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists. The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitDynaivity to antigens.

Abstract: The invention provides compositions and methods for regulating microRNA (miRNA) biogenesis. The invention also relates to compositions and methods for treating or preventing cancer in a subject in need thereof.

Abstract: It is disclosed herein that cultured primary placental human trophoblast (PHT) cells are highly resistant to infection by a number of disparate viruses, and confer this resistance to non-placental recipient cells by exosome-mediated delivery of microRNAs (miRs). PHT cells express high levels of unique, primate-specific miRNAs, expressed from the chromosome 19 miRNA cluster (C19MC). It is further disclosed herein that C19MC miRNAs are packaged within PHT-derived exosomes and attenuate viral replication in recipient cells by inducing autophagy. Thus, provided herein are methods of inhibiting, treating or preventing microbial infections by administering one or more miRs of the C19MC. Also provided are methods of inducing autophagy in a cell by contacting the cell with one or more miRs of the C19MC.

Abstract: Described herein are methods of triplex-induced apoptosis, in which multiple triplexes are formed in cells in which gene amplification has occurred (cells comprising/characterized by at least one amplified gene), referred to as target cells, and apoptosis is induced in the target cells.

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: Provided herein are RNAi agents for inhibition of Chikungunya virus. The present disclosure provides RNAi agents for inhibition of Chikungunya virus, particularly by targeting the E2 gene and nsP1 gene or both of the Chikungunya virus; the RNAi agents comprising of the entire nucleotide sequence set forth is SEQ ID 1 or SEQ ID 5 or combination thereof; or comprising of 15 or more contiguous nucleotides as set forth is SEQ ID 1 or SEQ ID 5 or combination thereof along with the addition nucleotides from the contiguous region of the E2 and nsP1 target gene. The invention further provides a RNAi composition for reducing the E2 protein and nsP1 protein level of Chikungunya virus and inhibition of Chikungunya virus replication. The combination of RNAi agents provides an excellent therapeutic composition for treatment of Chikungunya virus infection.

Abstract: The invention includes a method of treating an intraocular disorder in a mammal, the method comprising administering to the mammal a Very Late Antigen-4 (VLA-4) antagonist for the treatment of selected ocular disorders.

Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the Serpina1 gene, and methods of using such RNAi agents to inhibit expression of Serpina1 and methods of treating subjects having a Serpina1 associated disease, such as a liver disorder.

Abstract: A complex includes RNA and a positively charged modified polysaccharide selected from starch, amylose, amylopectin, galactan, chitosan, or dextrin. The complex can be formed into a pharmaceutical composition. The complex can be used in methods for RNA transfection, gene therapy and treatment of a disease, disorder or condition. The positively charged modified polysaccharide can be used in connection with RNA transfection into cells.