Abstract: Provided herein are methods for the prevention and treatment of cardiovascular diseases and disorders in a subject diagnosed as having suffered a cerebrovascular injury by administering agents that contain or induce the expression of microRNA-126.

Abstract: The presently disclosed subject matter relates to isolated compositions and methods for treating and/or preventing sepsis and inflammatory conditions, such as Acute Respiratory Distress Syndrome (ARDS). In some embodiments, the presently disclosed subject matter relates to endothelial progenitor cell-derived exosomes to treat and/or prevent sepsis and inflammatory conditions, such as Acute Respiratory Distress Syndrome (ARDS). The endothelial progenitor cell-derived exosomes can be modified to overexpress one or more miRNAs.

Abstract: The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications.

Abstract: The present application provides materials and methods for treating a patient with one or more conditions associated with ANGPTL3 whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of ANGPTL3 gene in a cell by genome editing.

Abstract: A method for treating a patient suffering from multiple sclerosis, including progressive forms of multiple sclerosis, comprising periodically administering a pharmaceutical composition comprising a therapeutically effective amount of OLIGONUCLEOTIDE I to the patient, thereby treating the patient.

Abstract: The present invention relates to a therapeutic antisense oligonucleotide which binds to exon 51 of the human dystrophin pre-mRNA to induce exon skipping, and conjugates and compositions thereof for the treatment of DMD.

Abstract: The present invention relates to a composition comprising an oligomeric compound comprising one or more tricyclo-deoxyribonucleic acid (tc-DNA) nucleosides and one or more lipid moiety, wherein said one or more lipid moiety is covalently linked to said oligomeric compound either directly or via a spacer, and wherein preferably said oligomeric compound comprises from 5 to 40 monomer subunits, as well as pharmaceutical compositions thereof and their uses in the prevention or treatment of neuromuscular or musculoskeletal diseases such as Duchenne muscular dystrophy or Steinert disease.

Abstract: An antibody or Fab fragment, wherein at least one amino group of the N-terminal amino acid of the light chain and/or of the N-terminal amino acid of the heavy chain is bound by an amidic bond to a molecule comprising a fluorophore group A, wherein said bond constitutes at least 70% of the total binding of said molecule to said antibody or Fab.

Abstract: The invention relates to double stranded ribonucleic acid (dsRNA) compositions targeting a glucokinase (GCK) gene, as well as methods of inhibiting expression of a glucokinase (GCK) gene, and methods of treating subjects having a glycogen storage disease (GSD), e.g., type Ia GSD.

Abstract: Novel oligonucleotides that enhance silencing of the expression of a gene containing a single nucleotide polymorphism (SNP) relative to the expression of the corresponding wild-type gene are provided. Methods of using novel oligonucleotides that enhance silencing of the expression of a gene containing a SNP relative to the expression of the corresponding wild-type gene are provided.

Abstract: The present invention relates to a double-helix oligonucleotide construct comprising a double-stranded miRNA and a composition for preventing or treating cancer comprising the same. More particularly, the present invention relates to a double-helix oligonucleotide construct comprising miR-544a characterized by a method that effectively inhibits the proliferation of cancer cells or induces a voluntary death of cancer cells, and an anticancer composition comprising the construct.

Abstract: A non-viral delivery complex comprising a cationic core which is a nanoparticle comprising a peptide having a polycationic nucleic acid binding component, a cleavable spacer element and a cell surface receptor binding component; a nucleic acid and optionally a cationic lipid; and an anionic liposomal coating surrounding the cationic core, said coating comprising lipids from a subject's cells. Also related formulations, uses and methods.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of GFAP RNA in a cell or subject, and in certain instances reducing the amount of GFAP in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a leukodystrophy. Such symptoms and hallmarks include motor delays, cognitive delays, paroxysmal deterioration, seizures, vomiting, swallowing difficulties, ataxic gait, palatal myoclonus, autonomic dysfunction, and presence of intra-astrocytic inclusions called Rosenthal fibers. Such leukodystrophies include Alexander Disease.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting PNPLA3 expression, which may be useful for treating, preventing, or ameliorating a disease associated with PNPLA3.

Abstract: Novel oligonucleotides that enhance silencing of the expression of a gene containing a single nucleotide polymorphism (SNP) relative to the expression of the corresponding wild-type gene are provided. Methods of using novel oligonucleotides that enhance silencing of the expression of a gene containing a SNP relative to the expression of the corresponding wild-type gene are provided.

Abstract: A nanoparticle activity sensor containing a reporter and at least one tuning domain that modifies a distribution or residence time of the activity sensor when administered to a patient. When administered to the patient, the activity sensor enters cells or tissue where it is cleaved by enzymes specific to a physiological state such as a disease to release a detectable analyte. The tuning domains include molecular structures that modulate distribution or decay by protecting the particle from premature cleavage and indiscriminate hydrolysis, shielding the particle from immune detection and clearance, or by targeting the particle to specific tissue, bodily fluids, or cell types.

Abstract: The invention relates to methods for increasing plant yield, and in particular grain yield by reducing or abolishing the expression and/or activity of OTUB1 in a plant. Also described are genetically altered plants characterised by the above phenotype and methods of producing such plants.

Abstract: A method of skipping a target exon of a gene of interest in a genome uses CRISPR-Cas and guide RNA. The guide RNA contains a spacer sequence such that the site of cleavage by the CRISPR-Cas is positioned within 80 bases from the splice donor site immediately before the target exon or the splice acceptor site immediately after the target exon.

Abstract: In some aspects, the disclosure relates to compositions and methods for treating fibrodysplasia ossificans progressiva (FOP) in a subject. In some aspects, the disclosure provides isolated nucleic acids, and vectors such as rAAV vectors, configured to express transgenes that inhibit (e.g., decrease) expression of mutated AVCR1 gene in muscle cells or connective tissues.

Abstract: The present specification provides a drug that causes highly-efficient skipping of exon 50 in the human dystrophin gene. The present specification provides an antisense oligomer which induces skipping of exon 50 in the human dystrophin gene.

Abstract: The present invention relates to a polynucleotide comprising a Nuclear factor of activated T-cells (NFAT) binding site sequence and a reverse complement of said NFAT binding site sequence separated by a spacer sequence, to said polynucleotide for use in treating and/or preventing disease, and to viral particles, compositions, and uses related thereto. The present invention further relates to a polynucleotide comprising a Nuclear factor of activated T-cells (NFAT) binding site sequence and a reverse complement of said NFAT binding site sequence for use in treating and/or preventing an NFAT-mediated disease.

Abstract: The present technology relates, in part, to long double-stranded RNA (dsRNA) (e.g., 30 or more base pairs) that inhibits gene expression.

Abstract: Stromal Derived Factor-1 (SDF-1) is a small, naturally occurring, potent chemokine with inherent angiogenic, neurogenic, anti-apoptotic protein, which is also a potent stem cell chemoattractant, cardiovascular disease, and other metabolic disturbances. The present invention provides methods for treating erectile dysfunction in a male subject comprising administering to the major pelvic ganglion supplying the cavernous nerves subject compositions comprising SDF-1. SDF-1 promotes stem cell activation, to the major pelvic ganglion supplying the cavernous nerves, helps cell preservation, and prevents adverse penile remodeling. It can be administered as a protein or by gene therapy including but not limited to plasmid DNA, viral transduction, or nanoparticle delivery directly to the penis or to the neurovascular bundle or other pelvic nerve structures during the time of surgery, or before injury, or to treat existing erectile dysfunction.

Abstract: The present invention relates to pharmaceutical compositions for preventing or treating pulmonary metastasis of cancer. More specifically, the present invention relates to compositions that enhance anti-cancer immunity of the lung rather than induce death of advanced cancer, thus being effective in inhibiting, preventing or treating pulmonary metastasis of cancer.

Abstract: The present invention relates to a method for treating a Leber congenital amaurosis in a patient harbouring the mutation c.2991+1655 A>G in the CEP290 gene, comprising the step of administering to said patient at least one antisense oligonucleotide complementary to nucleic acid sequence that is necessary for preventing splicing of the cryptic exon inserted into the mutant c. 2991+1655 A>G CEP290 mRNA.

Abstract: Provided is a modified double-stranded oligonucleotide, in which the sense strand comprises a nucleotide sequence 1, the anti-sense strand comprises a nucleotide sequence 2, the nucleotide sequences 1 and 2 are both 19 nucleotides in length, and in the direction from 5? end to 3? end, nucleotides at positions 7, 8 and 9 of the nucleotide sequence 1 and nucleotides at positions 2, 6, 14 and 16 of the nucleotide sequence 2 are all fluoro-modified nucleotides, and each nucleotide at other positions is independently one of non-fluoro-modified nucleotides. Further provided are a pharmaceutical composition and a conjugate comprising the oligonucleotide, and pharmaceutical use thereof.

Abstract: Linear covalently closed vectors, and compositions and methods for making same.

Abstract: The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the HAO1 gene, and methods of using such RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1.

Abstract: The present disclosure provides a cell separation apparatus for a bioreactor. The cell separation apparatus may be disposed outside the bioreactor and in fluid connection with the bioreactor, the cell separation apparatus may be in a shape of a box body, the cell separation apparatus may include a liquid buffer device including a first liquid cavity disposed in the box body; a filter device including a filter channel and a filter membrane disposed in the box body, the filter membrane may be disposed above the filter channel; and a first liquid channel may be configured in the box body to facilitate a fluid communication between the first liquid cavity and the filter channel. A power system for filtering and microfluidic channels are integrated in the cell separation apparatus that is of a box shape, thereby reducing the volume and production cost thereof.

Abstract: The invention relates to saRNA targeting an HNF4a transcript and therapeutic compositions comprising said saRNA. Methods of using the therapeutic compositions are also provided.

Abstract: The disclosure provides polynucleotides encoding a polypeptide including a morpholino linker. In some embodiments, the polynucleotides of the invention have increased stability compared to wild-type polynucleotides.

Abstract: The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the angiotensinogen (AGT) gene, and methods of using such RNAi agents to inhibit expression of AGT and methods of treating subjects having an AGT-associated disorder, e.g., hypertension.

Abstract: Provided are compositions comprising an oligonucleotide that targets Angiopoietin-like 4 (ANGPTL4). The oligonucleotide may include a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein are methods of treating a metabolic or cardiovascular disorder by providing an oligonucleotide that targets ANGPTL4 to a subject in need thereof.

Abstract: Compositions and methods for treating cancer in a subject in need thereof are described that includes administering a therapeutically effective amount of an oligonucleotide that specifically hybridizes to MALAT1.

Abstract: Disclosed herein are compounds, compositions, and methods for decreasing TIGIT mRNA and protein expression. Such methods are useful to treat, prevent, or ameliorate TIGIT associated diseases, disorders, and conditions.

Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose. The inclusion of such a monomer can allow for modulation of a property of the iRNA agent into which it is incorporated, e.g., by using the non-ribose moiety as a point to which a ligand or other entity, e.g., a lipophilic moiety. e.g., cholesterol, is is directly, or indirectly, tethered. The invention also relates to methods of making and using such modified iRNA agents.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: A compound of general formula (I) or (II), wherein Rn and Rm independently represent a C3-C27 aliphatic group, R1 to R4, which may be the same or different at each occurrence, represent hydrogen or a C1-C8 alkyl group, X1 and X2, which may be the same or different at each occurrence, represent a linear or branched divalent hydrocarbon radical with 1 to 24 carbon atoms which can be optionally substituted and/or interrupted by one or more heteroatoms or heteroatom containing groups, and R5 and R6, which may be the same or different at each occurrence, represent a group selected from —O?, -Alk-CH(OH)—CH2—SO3— and -Alk-CO2— wherein Alk represents an alkylene group.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: The present disclosure relates to compounds and compositions containing 5?-phosphoramidite nucleoside monomers of formulae (I) and (II), and methods of making and use, wherein the substituents are as defined in the appended claims.

Abstract: The present invention relates to products and compositions and their uses. In particular the invention relates to nucleic acid products that interfere with the TMPRSS6 gene expression or inhibits its expression and therapeutic uses such as for the treatment of hemochromatosis, porphyria and blood disorders such as ?-thalassemias, sickle cell disease and transfusional iron overload or myelodysplastic syndrome.

Abstract: The invention relates to saRNA targeting an HNF4a transcript and therapeutic compositions comprising said saRNA. Methods of using the therapeutic compositions are also provided.

Abstract: The present invention relates to a targeting-type capsule for drug delivery systems. The present invention addresses the problem of providing a capsule for drug delivery systems by utilizing the reactivity of a thiol with an alkyl halide, wherein the capsule comprises a silole-containing carbosilane dendrimer and a labeling protein containing a target recognition site (e.g., green fluorescent protein), can include a biological polymer or another molecule therein, and can deliver the biological polymer or the like selectively into a target cell.

Abstract: The present invention relates to methods of treating, preventing or managing intestinal fibrosis by inhibiting SMAD7. The invention is also directed to methods of monitoring effectiveness of treatment or management of intestinal fibrosis using a SMAD7 antisense oligonucleotide, as well as methods of regulating SMAD7 antisense oligonucleotide treatment, based on analysis of Transforming Growth Factor-? (TGF-?) levels, ?-Smooth Muscle Actin (a-SMA) levels, and/or phosphorylated Mothers Against Decapentaplegic Homolog 3 (p-SMAD3) levels.

Abstract: The present invention relates to the field of biomedicine, particularly to double-stranded RNA molecules targeting CKIP-1 and uses thereof, particularly to use of the double-stranded RNA molecules for the treatment of inflammatory diseases such as arthritis, particularly rheumatoid arthritis.

Abstract: The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Abstract: Provided are antisense oligomers targeted against bacterial mRNAs and other macromolecules associated with a biochemical pathway and/or cellular process, and related compositions and methods of using the oligomers and compositions to treat an infected mammalian subject, for example, as primary antimicrobials or as adjunctive therapies with classic antimicrobials.

Abstract: Methods of using B2 or Alu nucleic acids, or antisense oligonucleotides that modulate the EZH2/B2 or EZH2/Alu interaction and have the capacity to alter cleavage of B2 and Alu RNA, for increasing or decreasing cell and organismal viability.

Abstract: The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

Abstract: The present invention provides a phosphorothioate-modified oligonucleotide comprising a structure shown below: The present invention also provides a phosphorothioate-modified oligonucleotide comprising a structure having formula (CIII):