Abstract: The present disclosure relates to the field of medicine. In particular, it relates to novel antisense oligonucleotides that prevent or reduce exon 8 skipping in the SLC26A4 gene during pre-mRNA splicing, and their use in the treatment of Pendred Syndrome.

Abstract: The disclosure relates to antigen detection reagents and related methods, systems, and kits. The reagents comprise an antigen-binding molecule conjugated to an inorganic component. In some embodiments, the inorganic component possesses catalytic functionality to provide a detectable signal. In some embodiments, the catalytic inorganic component is or comprises a bimetallic nanoparticle. In other embodiments, the inorganic component is a nanoflowers that provides a physical scaffold onto which the antigen-binding component and a reporter component can be loaded, resulting in augmented antigen-binding and reporting capabilities.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for modulating SMN2 RNA and/or protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disorder. Such symptoms include reduced muscle strength; inability or reduced ability to sit upright, to stand, and/or walk; reduced neuromuscular activity; reduced electrical activity in one or more muscles; reduced respiration; inability or reduced ability to eat, drink, and/or breathe without assistance; loss of weight or reduced weight gain; and/or decreased survival.

Abstract: Disclosed are methods for modulating splicing of Ataxin 3 mRNA in an animal with modified oligonucleotides. Such compounds and methods are useful to treat, prevent, or ameliorate spinocerebellar ataxia type 3 (SCA3) in an individual in need thereof.

Abstract: Disclosed herein are novel compositions, methods, and systems for determining whether a subject has, or is at risk of developing, or is at a given stage of a condition afflicting a tissue of interest, or determining the tissue or cell provenance of a biological sample, based on expression level of one or more of the novel miRNA and isomiR sequences disclosed herein. The compositions, methods, and systems described herein can be used to diagnose a disease or disorder, or prognose a given stage and/or progression of the disease or disorder, or determine the identity of the tissue or cell in a sample. In some embodiments, the compositions, methods, and systems described herein can be used to develop a treatment for the disease or disorder. For example, in some embodiments, the novel miRNAs can be used as therapeutics for treatment of a disease or disorder.

Abstract: The present invention provides industrially suitable processes for preparing intermediates in the production of substituted polycyclic pyridone derivatives having a cap-dependent endonuclease inhibitory activity. In the process as shown below, wherein each symbol is as defined in the specification, an optically active substituted tricyclic pyridone derivative of the formula (VII) is obtained in high yield and high enantioselectivity by subjecting a compound of the formula (III) or (VI) to intramolecular cyclization with controlling stereochemistry to obtain a compound of the formula (IV) having a removable functional group on an asymmetric carbon, and then removing the functional group thereof.

Abstract: A substituted pyrimidine piperazine compound and uses thereof, and a pharmaceutical composition containing the compound and uses thereof. Wherein the compound has Formula (I), or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. The substituted pyrimidine piperazine compound and the pharmaceutical composition containing the compound can be used to inhibit 5-hydroxytryptamine reuptake and/or activate the 5-HT1A receptors. Also, a method of preparing such compounds and pharmaceutical compositions, and uses thereof in the treatment of central nervous system dysfunction.

Abstract: Aptamers having a G-quadruplex structure that bind specifically to the most commonly used azole-class antifungal drugs, biosensors that comprise those aptamers, and invitro methods for determining the level of one of those drugs utilizing those aptamers or biosensors.

Abstract: This application relates to potent oligonucleotides useful for reducing HBsAg expression and treating HBV infections.

Abstract: The present invention relates to methods for treating and preventing ophthalmological disease and disorders, comprising administering Antagonist A or another pharmaceutically acceptable salt thereof, optionally in combination with another treatment, to a subject in need thereof. The present invention also relates to methods for treating and preventing ophthalmological disease and disorders, comprising administering an anti-C5 agent (e.g., ARC1905), optionally in combination with another treatment, to a subject in need thereof.

Abstract: Provided is an oligonucleotide conjugate comprising an oligonucleotide and two or more linearly connected asialoglycoprotein receptor-binding molecules attached to the oligonucleotide, wherein the oligonucleotide comprises a locked nucleoside analog having a bridging structure between the 4? and 2? positions, is complementary to a human PCSK9 gene, and has inhibitory activity on the expression of the human PCSK9 gene. The oligonucleotide conjugate of the present invention can be used in the field of pharmaceutical products, in particular, the field of the development and production of therapeutic agents for diseases associated with a high LDL cholesterol level.

Abstract: The invention relates to double stranded oligonucleotide complexes comprising an antisense oligonucleotide (AON) and a complementary sense oligonucleotide (SON), for use in the deamination of a target adenosine in a sense target RNA sequence in a cell by an ADAR enzyme, wherein at least the nucleotide in the AON that is directly opposite the target adenosine in the target RNA sequence does not have a 2?-O-alkyl modification and the SON comprises nucleotides that are at least complementary to all nucleotides in the AON that do not have a 2?-O-alkyl modification. The invention further relates to methods of RNA editing using the AON/SON complexes of the invention.

Abstract: Disclosed herein are methods for treating a subject afflicted with a cancer having an activating RET alteration by administering an effective amount of a selective RET inhibitor, e.g., Compound 1 or pharmaceutically acceptable salts thereof, including, e.g., administering an amount of 60 mg to 400 mg of the selective RET inhibitor once daily.

Abstract: Provided is a nucleic acid strand that can efficiently deliver an antisense oligonucleotide into the body, particularly a nucleic acid complex comprising a first nucleic acid strand and a second nucleic acid strand, wherein the first nucleic acid strand includes a base sequence that is capable of hybridizing with at least a portion of a target transcription product, and exerts an antisense effect on the target transcription product; the second nucleic acid strand includes a complementary region having a base sequence complementary to the first nucleic acid strand and at least one overhang region located on the 5? and/or 3? side of the complementary region; and the first nucleic acid strand is annealed to the complementary region in the second nucleic acid strand.

Abstract: The invention relates methods of using RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1.

Abstract: The present invention relates to a N2,N4-diphenylpyrimidin-2,4-diamine derivative, a method for preparing the same, and a pharmaceutical composition for the prevention or treatment of cancer, containing the same as an active ingredient. The derivative shows a relatively weak EGFR activity inhibitory effect on wild-type EGFR, a high inhibitory ability on EGFR mutation, and a high inhibitory ability on even FLT3 and FLT3 mutation, and thus, can be effectively used for the treatment of cancer with EGFR mutation or cancer with FLT3 or a mutation thereof, and the derivative shows a synergy effect at the time of combination administration, and thus can be effectively used for the treatment of combination administration.

Abstract: The present invention includes an engineered cell comprising a chimeric antigen receptor (CAR) further comprising a nucleic acid molecule comprising a suicide gene comprising a ligand binding domain and a suicide domain wherein the ligand binding domain is capable of binding to radiolabeled tracer or a small molecule suicide switch. This invention also includes methods for inducing apoptosis of an engineered cell, methods for assessing the efficacy or toxicity of an adoptive cell therapy in a subject, methods for detecting the quantity of engineered T cells in a subject, methods for monitoring an immunotherapy treatment in a subject and methods of imaging engineered T cells in a subject. In some embodiments, the imaging is performed via Positron Emission Topography (PET). This invention further includes a chemical inducer of dimerization (CID), wherein the CID is a Bis-Trimethoprim (Bis-TMP).

Abstract: Certain embodiments provide RNA nanostructure (e.g., comprising one single-stranded RNA (ssRNA) molecule, wherein the RNA nanostructure comprises at least one paranemic cohesion crossover), as well as compositions and methods of use thereof. In certain embodiments, such RNA nanostructures are immuno-modulatory (e.g., immuno-stimulatory).

Abstract: A method of preparing a universal blood product comprising obtaining a blood product; contacting the blood product with (i) hydroxyapatite; (ii) a carbonaceous material comprising at least a mixture of a first carbon particle having macroporous size ? and a second carbon particle having macroporous size ?; and (iii) at least one support matrix chemically associated with an antigenic determinant. to form a cleansed product; and recovering the cleansed product. A method of preparing a universal blood product comprising obtaining a blood product; contacting the blood product with (i) hydroxyapatite; (ii) a carbonaceous material comprising at least a mixture of a first carbon particle having macroporous size ? and a second carbon particle having macroporous size ?; and (iii) at least one support matrix chemically associated with an antigenic determinant. to form a cleansed product; wherein at least one of the hydroxyapatite, carbonaceous material and support matrix is functionalized.

Abstract: The invention relates to the use of a lectin that recognizes the fucose ? 1-2 galactose unit, as a first means for labeling and optionally a second means for labelling colorectal cancer stem cells, in particular a lectin that recognizes the T antigen, in order to carry out a method for the detection and optionally isolation of colorectal cancer stem cells, a method for the detection and optionally isolation of colorectal cancer stem cells for research purposes, and a method for the in vitro diagnosis of colorectal cancer recurrence risk and/or aggressiveness so as to define a prognostic value in order to make colorectal cancer therapy adjustments, as well as a kit comprising a lectin that recognizes the fucose ? 1-2 galactose unit and a lectin that recognizes the T antigen.