Abstract: Disclosed herein are high Tm RNA nanostructures that can be composed of one or more modules or motifs to build RNA nanostructures with or without layers. The RNA nanostructures can have a core domain and three or more double-stranded arms and formulations thereof to conjugate high copy numbers of therapeutics, pH responsive or enzyme cleavable drug cargo. Also described herein is a design strategy for generation of synthetic RNA oligonucleotides that can self assemble into highly thermostable RNA structures. Also described herein are uses of the RNA nanostructures described herein.

Abstract: The present disclosure provides in vitro methods for predicting a compound's ability to inhibit multinucleate cell production resulting from post-mitotic cell fusion during a process of Daughter Number Variation (DNV) in mitosis. Compounds identified by this method can be used in cancer treatment, either alone or in combination with other known cancer drugs. The present invention also provides methods of personalized cancer treatment for a patient having a malignant tumor.

Abstract: The present disclosure provides a preparation method of tofacitinib citrate, which comprises the following steps: passing an intermediate TOF-2 into hydrogen at a normal pressure in the presence of a catalyst to obtain an intermediate TOF-3; in the presence of a solvent and a base, under a reduced pressure of ?490 mmHg to ?760 mmHg, and at a temperature of 10° C. to 25° C., reacting TOF-3 with ethyl cyanoacetate to generate an intermediate TOF-4; heating and dissolving TOF-4 and citric acid in a solvent, and performing separation by cooling to obtain tofacitinib citrate. The present disclosure obtains tofacitinib citrate with high yield, high purity and low impurities by changing a gas flow rate and a reaction temperature and pressure of a hydrogenation reaction. Therefore, the preparation method is suitable for industrial production.

Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.

Abstract: Among other things, the present disclosure provides designed PNPLA3 oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or N patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc.

Abstract: The present invention relates to nucleic acids for inhibiting expression of a target gene in a cell, comprising at least one duplex region that comprises at least a portion of a first strand and at least a portion of a second strand that is at least partially complementary to the first strand, wherein said first strand is at least partially complementary to at least a portion of RNA transcribed from said target gene to be inhibited. The first strand of the nucleic acid has a terminal 5? (E)-vinylphosphonate nucleotide that is linked to the second nucleotide in the first strand by a phosphodiester linkage.

Abstract: Disclosed herein are embodiments of nanohoop compounds and conjugates thereof that can be used myriad biological applications. The nanohoop compounds described herein can exhibit beneficial properties that are useful in biotechnology, such as a fluorescent tag, probe, or label.

Abstract: A method for promoting conversion of cells into cardiomyocytic tissue is carried out by contacting fibrotic tissue (e.g., scar tissue) with a microRNA oligonucleotide or combination of microRNA oligonucleotides. The methods lead to direct reprogramming of fibroblasts to cardiomyocytes or cardiomyoblasts.

Abstract: Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject.

Abstract: This application relates to therapeutic siRNA agents and methods of making and using the agents.

Abstract: The invention concerns a trans-splicing RNA (tsRNA) molecule comprising one or multiple unstructured binding domains; a cell or vector comprising said tsRNA; and a method for killing cells or treating a disease using said tsRNA.

Abstract: The invention relates to acid addition salts of ridinilazole and processes for the preparation of ridinilazole using these acid addition salts. In addition, the present invention relates to processes for the preparation of ridinilazole in pure form using acid addition salts of ridinilazole as process intermediates.

Abstract: The description provides a molecular switch comprising at least two nanoparticles, wherein a first nanoparticle comprises DNA and/or RNA oligonucleotides, and a second nanoparticle which is complementary to the first nanoparticle comprises reverse complementary DNA and/or RNA oligonucleotides of the first nanoparticle; wherein the complementary nanoparticles interact under physiological conditions leading to thermodynamically driven conformational changes in the first and second nanoparticles leading to their re-association to release one or more duplexes comprising said DNA and/or RNA oligonucleotides and the reverse complementary DNA and/or RNA oligonucleotides, and wherein the nanoparticles are not rings and have no single stranded toeholds.

Abstract: One aspect of the present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2?-fluoro modifications, and the sense strand of the dsRNA molecule comprises ligand, wherein the ligand is an ASGPR ligand. Other aspects of the invention relates to pharmaceutical compositions comprising these dsRNA molecules suitable for therapeutic use, and methods of inhibiting the expression of a target gene by administering these dsRNA molecules, e.g., for the treatment of various disease conditions.

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 LPA gene expression or inhibit its expression, preferably for use as treatment, prevention or reduction of risk of suffering cardiovascular disease such as coronary heart disease or aortic stenosis or stroke or any other disorder, pathology or syndrome linked to elevated levels of Lp(a) particles.

Abstract: The present invention concerns the use of antisense oligonucleotides (AON) capable of inhibiting expression of dynamin 2, advantageously human dynamin 2, for use in the treatment of Charcot-Marie-Tooth disease (CMT) and centronuclear myopathies (CNM).

Abstract: Provided are an additive and a surface treatment agent capable of suppressing agglutination of latex particles contained in a reagent for a latex agglutination reaction during storage of the reagent although a synthetic polymer is contained as an active component. An additive is to be added to latex particles used in a reagent for a latex agglutination reaction. The latex particles have not been subjected to blocking treatment. The additive includes a polymer containing more than 60% by mass and 99% by mass or less of hydrophilic repeating units (A) relative to all repeating units and 1% by mass or more and less than 40% by mass of hydrophobic repeating units (B) relative to all repeating units, and having a weight average molecular weight of 3,000 or more.

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 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: The present invention relates to a method for measuring the cholesterol uptake capacity of lipoproteins. The present invention also relates to a reagent kit for measuring the cholesterol uptake capacity of lipoproteins. The present invention further relates to a tagged cholesterol which can be used in the method and the reagent kit.