Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Abstract: Provided herein are DNA aptamers targeting AXL receptor kinase. The DNA aptamers may comprise a thiophosphate backbone and be chemically modified. Further provided herein are methods of use thereof for the treatment of a disease or disorder, such as cancer.

Abstract: Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.

Abstract: It is disclosed herein that ssAAV and scAAV vectors of the same serotype administered by injection into the cerebrospinal fluid (CSF) via the intracerebroventricular (ICV) or intrathecal (cisternal or lumbar) route exhibit different cellular tropisms in the central nervous system. Thus, a subject can be treated by injection into the CSF of ssAAV or scAAV vector encoding a therapeutic protein, such as an ssAAV9 or scAAV9 vector. The therapeutic protein can be targeted to specific cells using these vectors. In some embodiments, scAAV9 is utilized to achieve superior transduction in the hippocampus, cerebellum and cerebral cortex where both neurons, particularly Purkinje neurons, and glial cells (such as astrocytes) are transduced. In other embodiments, ssAAV9 is utilized to minimize transduction of astrocytes. In further embodiments, an immunosuppressive agent is also administered to the subject.

Abstract: Provided are compositions and methods for use of hornerin-binding molecules, including peptides and antibodies. In some embodiments, the presently disclosed subject matter provides compositions that include horning-binding molecules, including but not limited to peptides, uses for the disclosed compositions, including in methods for treating tumors, methods for increasing the survival of subject with tumor, methods for suppressing tumor growth in subjects, methods for reducing tumor vascularity in subjects, methods for treating diseases, disorders, and/or conditions associated with undesirable hornerin expression; methods for modulating hornerin biological activities, methods for imaging cells, tissues, and/or organs that expresses hornerin, and methods for delivering active agents to cells, tissues, and/or organ that expresses hornerin.

Abstract: The present invention relates to method of modulating the level of expression of an endogenous gene in a cell, the method comprising inserting a heterologous microRNA (miRNA) response element (MRE) into the 3?-untranslated region (3?-UTR) of the gene. The binding of endogenous miRNAs to the MRE results in or leads to a repression of the level of expression of the gene. The invention also relates to cells and transgenic animals whose endogenous genes comprise heterologous MRE in their 3?-UTRs.

Abstract: The present invention relates to the discovery that the expression levels of some microRNAs (miRNAs) can use a diagnostic signature to predict transplant outcomes in a transplant recipient. Thus, in various embodiments described herein, the methods of the invention relate to methods of diagnosing a transplant subject for acute rejection such as acute cellular rejection (ACR), methods of predicting a subject's risk of having or developing ACR and methods of assessing in a subject the likelihood of a successful or failure minimization of immunosuppression therapy (IST) dosage from standard ranges.

Abstract: The present invention features antisense oligonucleotides (AONs) for the treatment of diseases and disorders associated with the deleterious effects of transposable element insertion (e.g., long interspersed nuclear element-i (LINE-1), Arthrobacter luteus element (Alu), short interspersed nuclear element variable number tandem repeat Arthrobacter luteus element (SINE-VNTR-Alu) or (SVA), or endogenous retrovirus (ERV). In one aspect, the invention provides one or more antisense oligonucleotides complementary to a transposable element present in an intronic sequence within a gene. In another aspect, the invention provides a method for treating a subject having a genetic disorder associated with the insertion of a transposable element, the method involving administering to the subject one or more antisense oligonucleotides of any aspect delineated herein.

Abstract: Disclosed are polynucleotide constructs having a strand linked to a moiety carrying one or more auxiliary moieties. Also disclosed are polynucleotide constructs interrupted with a sugar analogue, and polynucleotide constructs with stereochemical{circumflex over (?)} enriched phosphorothioates. The polynucleotide constructs may be provided as hybridized polynucleotide constructs. Also featured are methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell by contacting the cell with the disclosed polynucleotide construct or hybridized polynucleotide construct.

Abstract: The specification discloses a method of treating muscular disorders such as muscular dystrophy comprising periodically administering an inhibitory oligonucleotide to human CD49d ((the alpha 4 chain of VLA-4).

Abstract: The present invention refers to immunosuppression-reverting oligonucleotides comprising 12 to 18 nucleotides, wherein at least one of the nucleotides is modified, and the oligonucleotide hybridizes with a nucleic acid sequence of an ectonucleotidase (NTPdase; CD73) of SEQ ID NO.1 (human), wherein the oligonucleotide inhibits at least 50% of the CD39 expression. The invention is further directed to a pharmaceutical composition comprising such oligonucleotide.

Abstract: The present invention includes a composition and method for decreasing Bacillus anthracis virulence or toxicity comprising: at least one inhibitor that decreases an expression of one or more host genes selected from G6pc, Rgs1, Fosl2, Hcar2, Cxcl2 and Cxcl3, or Serpine1 (PAI-1).

Abstract: Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of a DMPK allele comprising a disease-associated-repeat. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Abstract: Some embodiments of the invention include a nucleic acid molecule comprising natural nucleotides, non-natural nucleotides, an LNA which comprises one or more RNA core molecules, or an RNA molecule which comprises more than one RNA core molecule. Some embodiments of the invention include a nucleic acid molecule comprising an RNA molecule which comprises more than one RNA core molecule. Other embodiments of the invention include a nucleic acid molecule comprising a DNA molecule encoding the RNA molecule (e.g., vector or viral vector). Other embodiments include compositions or pharmaceutical compositions that comprise the nucleic acid molecule. Some embodiments of the invention comprise reducing miR-143 in a cell. Other embodiments of the invention include methods to deliver a protein across the BBB. Other embodiments include methods for treating disease (e.g., LSD, neuronopathic disease, neurodegenerative disease, Hurler syndrome, or MPS I). Additional embodiments of the invention are also discussed herein.

Abstract: The present invention provides an oligonucleotide comprising the sequence 5?-GGAACAGTTCGTCCATGGC-3? (SEQ ID NO:2) for use in the treatment of inflammatory bowel disease in a human subject, wherein individual doses of from 100 mg to 350 mg of said oligonucleotide are administered to the subject on at least four separate occasions, wherein the separate occasions are each a week apart.

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: The present disclosure provides polynucleotide constructs for the modulation of target gene expression by aptamer-mediated ribonuclease cleavage of the target gene RNA and methods of using the constructs to modulate gene expression in response to the presence or absence of a ligand that binds the aptamer. The polynucleotide constructs contains a ribonuclease substrate sequence (e.g., an RNase P substrate) and a riboswitch comprising an effector region and an aptamer such that when the aptamer binds a ligand, target gene expression occurs.

Abstract: The invention provides a method of treating preeclampsia, fetal growth restriction (FGR or IUGR), obesity in pregnancy, post-partum cardiomyopathy (heart failure in mothers), cancer and diabetic retinopathy, cardiomyopathy, myocardial infarction, wet microdegeneration and other disorders where angiogenesis is aberrant either diminished or exacerbated, comprising modulating the activity of micro RNA (miRNA). Also provided are an MiRNA modulator or a combination thereof or functional fragments or homologues thereof for use in the treatment of preeclampsia, fetal growth restriction, obesity in pregnancy, cancer, and diabetic retinopathy, cardiomyocyte infarction, wet microdegeneration as well as other disorder where angiogenesis is aberrant either diminished or exacerbated. Methods of modulating angiogenesis and pharmaceutical compositions using miR-122, miR-374b or inhibitors of miR-152 or miR195 are also provided together with methods of diagnosis using the miRNAs.

Abstract: The invention is directed to compositions and methods for increasing the pH of a melanosome in a melanocyte, darkening skin or hair pigmentation, or treating a disease associated with decreased melanin comprising administering a soluble adenylyl cyclase (sAC) inhibitor and/or an exchange protein activated by cyclic AMP (EPAC) inhibitor to the melanocyte. The invention also provides compositions and methods for decreasing the pH of a melanosome in a melanocyte, lightening skin or hair pigmentation, or treating a disease associated with increased melanin comprising administering a sAC activator and/or an EPAC activator to the melanocyte.

Abstract: The present invention relates to a novel approach for treating cancer, which is based on targeting PD-L1 mRNA. The invention is directed to oligonucleotides comprising 10 to 20 modified or unmodified nucleotides complementary to specifically selected regions of the PD-L1.