Abstract: Compositions and methods for using nucleosome interacting protein domains to increase accessibility of programmable DNA modification proteins to target chromosomal sequences, thereby increasing efficiency of targeted genome/epigenetic modification in eukaryotic cells.

Abstract: Among the various aspects of the present disclosure is the provision of a NXTAR-derived oligonucleotides and uses thereof. An aspect of the present disclosure provides for a method of (i) suppressing androgen receptor (AR) expression, (ii) suppressing androgen receptor splice variants (including AR-V7) expression, (iii) treating cancer (e.g., prostate, breast, testis, ovarian, endometrial and skin) (iv) treating skin related diseases, such as androgenetic alopecia and acne vulgaris in a subject comprising administering to the subject a NXTAR-derived oligonucleotide (oligo) (NXTAR is a lncRNA also known as LOC105373241).

Abstract: In the field of biomedical technology, a PIWI-interacting RNA piR-hsa-211106 is used to prepare a targeted therapeutic drug for inhibiting proliferation of lung adenocarcinoma cells. A mechanism is as follows: after the PIWI-interacting RNA piR-hsa-211106 is constructed into an agonist or a transformant, the agonist or the transformant inhibits a tricarboxylic acid cycle process by down-regulating an expression of a pyruvate carboxylase, inhibits an energy metabolism, promotes apoptosis of the lung adenocarcinoma cells, thus inhibits growth of the lung adenocarcinoma. The PIWI-interacting RNA piR-hsa-211106 directly acts on a target site and does not produce toxic and side effects and an off-target phenomenon. Large amounts of analysis and in-vivo and in-vitro experiments show that the PIWI-interacting RNA piR-hsa-211106 has high credibility and a remarkable treatment effect, and provides a new research direction for anti-tumor therapy of lung adenocarcinoma.

Abstract: The present technology comprises methods and RNA constructs for the targeted translation of a polypeptide of interest in a eukaryotic target cell, and to the use thereof in therapeutic clinical applications.

Abstract: This disclosure provides methods of treating a myelodysplastic syndrome (MDS) in a subject that is naive to treatment with an agent selected from a hypomethylating agent (HMA) and lenalidomide, or both. The method includes administering to the subject an effective amount of a telomerase inhibitor, such as e.g. imetelstat or imetelstat sodium. In some cases, the subject treated is classified as low or intermediate-1 IPSS risk MDS and/or have MDS relapsed/refractory to Erythropoiesis-Stimulating Agent (ESA).

Abstract: The present application relates to the field of cancer, particularly that of cancers with high MDM4 protein levels (such as melanoma, breast, colon or lung cancers, glioblastoma, retinoblastoma, etc.). It is shown herein that direct and selective inhibition of MDM4, e.g., by antisense RNA, leads to growth inhibition of cancer cells and sensitization to chemo or targeted therapies. Also provided are simple ways of determining which patients are most amenable for such treatment by comparing specific transcript levels.

Abstract: Provided herein are polynucleotides and CRISPR effector proteins configured to be covalently bound together in a CRISPR complex. The polynucleotides can be further modified to modulate the activity of the CRISPR complex. Modification of the polynucleotide and CRISPR effector protein can be used to improve the efficacy of target binding and/or cleavage.

Abstract: A novel network of tumorigenic prognostic factors is identified that plays a critical role in advanced pancreatic cancer (PC) pathogenesis. This interactome is interconnected through a central tumor suppressive microRNA, miR-198, which is able to both directly and indirectly modulate expression of the various members of this network to alter the molecular makeup of pancreatic tumors, with important clinical implications. When this tumor signature network is intact, miR-198 expression is reduced and patient survival is dismal; patients with higher miR-198 present an altered tumor signature network, better prognosis and increased survival. Further, according to the present disclosure, MiR-198 replacement reverses tumorigenicity in vitro and in vivo.

Abstract: An antiviral agent is provided, having a phosphorodiamidate morpholino oligomer with an antisense sequence to a portion of a genome of a strain of a coronavirus. The coronavirus may be SARS-CoV-2 or another ?CoV. The antiviral agent finds many uses, such as in a pharmaceutical composition, a method of treating coronavirus-mediated disease, a method of preventing coronavirus-mediated disease, a method of reducing or preventing the replication of coronavirus in a host cell, a method of controlling the spread of coronavirus in donated tissue, a treated tissue sample, and in the manufacture of a medicament for the treatment or prevention or coronavirus-mediated disease.

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 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: 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: 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 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: 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: 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.