The present application relates to a novel conjugate group linkable to a compound (such as a therapeutic compound), for use in directing the compound to a target in the body. The conjugate group disclosed herein can enable an expression-inhibitory oligonucleotide (such as a RNAi reagent) to target liver cells to regulate gene expression. The conjugate group disclosed herein has a variety of applications when linked to expression-inhibitory oligonucleotides, comprising applications in therapy, diagnosis, target verification, and genome development. A composition comprising the conjugate group disclosed herein can mediate expression of target nucleic acid sequences in liver cells (such as hepatocytes) when linked to expression-inhibitory oligonucleotides, and can be used for treatment of diseases or disorders responding to the gene expression or activity of cells, tissues, or organisms.

The present application relates to a novel conjugate group linkable to a compound (such as a therapeutic compound), for use in directing the compound to a target in the body. The conjugate group disclosed herein can enable an expression-inhibitory oligonucleotide (such as a RNAi reagent) to target liver cells to regulate gene expression. The conjugate group disclosed herein has a variety of applications when linked to expression-inhibitory oligonucleotides, comprising applications in therapy, diagnosis, target verification, and genome development. A composition comprising the conjugate group disclosed herein can mediate expression of target nucleic acid sequences in liver cells (such as hepatocytes) when linked to expression-inhibitory oligonucleotides, and can be used for treatment of diseases or disorders responding to the gene expression or activity of cells, tissues, or organisms.

The present specification discloses a urate oxidase-albumin conjugate, a preparation method thereof, a urate oxidase variant contained in the urate oxidase-albumin conjugate, and a preparation method thereof. The urate oxidase-albumin conjugate is characterized in that three or more albumins are conjugated to the urate oxidase variant through a linker, thereby improving half-life and reducing immunogenicity. In addition, the urate oxidase-albumin conjugate can be used to prevent or treat various diseases, disorders and/or indications caused by uric acid.

The present invention provides a compound exhibiting coronavirus 3CL protease inhibitory activity or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same. Furthermore, the present invention provides a crystalline form useful as an active pharmaceutical ingredient, and a pharmaceutical composition comprising the same.

A compound represented by Formula:

##STR00001##

, or a pharmaceutically acceptable salt thereof.

Provided herein are gene editing systems and/or compositions comprising RNA guides targeting LDHA for use in genetic editing of the LDHA gene. Also provide herein are methods of using the gene editing system for introducing edits to the LDHA gene and/or for treatment of primary hyperoxaluria (PH), and processes for characterizing the gene editing system.

The present invention concerns compounds and their use to treat cardiovascular disease, renal disease, thrombic disease, stroke, metabolic syndrome, cell proliferation, and ischemic cardiovascular disorders. Compounds of the present invention display significant potency as antagonists of 20-hydroxyeicosatetraenoic acid (20-HETE), and function as anti-hypertensive, anti-inflammatory, or anti-growth agents.

The present disclosure generally relates to metal-organic framework nanoparticles containing terminal phosphate-modified oligonucleotides, methods for making the same, and methods of using the same.

Compositions and methods relating to modulating thermogenic regulation are disclosed. The compositions and methods can be used to treat diseases or conditions such as obesity or cardiometabolic disorders such as type 2 diabetes mellitus, NAFLD and NASH. Compositions include an adipocyte-targeting composition that includes a therapeutic agent capable of modulating thermogenic regulation, a targeting element facilitating cellular uptake and delivery of the therapeutic agent to a targeted adipocyte, and liposomal particles comprising sphingomyelin, DMPC, and cholesterol, wherein the liposomal particles enhance intra-cellular penetration of the therapeutic agent and protect the therapeutic agent from degradation.

SCGB-based preparations and methods to use these preparations to protect the glycocalyx in medical, veterinary, and cosmetic applications are provided. The secretoglobins (SCGBs) are a family of small secreted globular proteins present in all mammals and sharing conserved structure and thought to share similar immunomodulatory functions. Heparan sulfate proteoglycan proteins (HSPGs) are expressed on the outer membranes of cells and have carbohydrate side chains that, together, make up the glycocalyx. The glycocalyx is a protective layer surrounding all cells, acting as a filter regulating the passage of nutrients into the cell and modifying cell signaling by external factors. There are two major families of HSPGs including syndecans and glypicans, plus several other HSPGs in all mammals. SCGBs bind to, and interact with, HSPGs to further modulate cell signaling and cellular responses to external factors.

Provided is a drug containing a liver targeting specific ligand and a thyroid hormone receptor agonist in its structure, which is a new drug structure formed by linking the liver targeting specific ligand with the thyroid hormone receptor agonist through a branched chain, a linker and a linking chain. Thyroid hormone receptors (TRs) are divided into two subtypes, TR-α and TR-β, wherein, TR-β is mainly expressed in liver, and TR-α is mainly expressed in heart, nervous system, etc. In certain embodiments, it is envisaged that the provided drug has the action of liver targeting, can specifically bring the thyroid hormone receptor agonist into liver, without entering heart and other issues, and may thereby avoid side effects caused by the action of the thyroid hormone receptor agonist on other issues, and maintain its therapeutic efficacy in the treatment of lipid metabolism disorders and related complications.