The present invention is directed to compositions and methods for treating hepatitis B virus infection. In particular, the present invention is directed to a combination therapy comprising administration of a therapeutic oligonucleotide targeting HBV and a TLR7 agonist for use in the treatment of a chronic hepatitis B patient.

Disclosed herein are oligonucleotides, such as nucleic acid inhibitor molecules, having a 4′-phosphate analog and methods of using the same, for example, to modulate the expression of a target gene in a cell. The phosphate analogs are bound to the 4′-carbon of the sugar moiety (e.g., a ribose or deoxyribose or analog thereof) of the 5′-terminal nucleotide of an oligonucleotide. Typically, the phosphate analog is an oxymethylphosphonate, where the oxygen atom of the oxymethyl group is bound to the 4′-carbon of the sugar moiety or analog thereof.

Disclosed are immune cell-selective small molecule IMPDH inhibitor compounds and methods of their synthesis and use to treat proliferative disorders.

Disclosed are immune cell-selective small molecule compounds that modulate certain immune cell-specific receptors and enzymes, and methods of their synthesis and use to treat proliferative disorders.

Fusosome compositions and methods are described herein.

The present disclosure relates to the use of PGC-1α expression to identify a subject that is conducive to treatment with a ma-485 inhibitor. In some aspects, the subject suffers from a disease or disorder associated with reduced PGC-1α expression. In some aspects, the PGC-1α expression is measured in the serum of the subject.

The present disclosure relates to the use of SIRT1 expression to identify a subject that is conducive to treatment with a miR-485 inhibitor. In some aspects, the subject suffers from a disease or disorder associated with reduced SIRT1 expression. In some aspects, the SIRT1 expression is measured in the serum of the subject.

Ivacaftor glycosides and methods of making ivacaftor glycosides are disclosed. Glycosyl transferases catalyze addition of one or more monosaccharides to ivacaftor to yield ivacaftor glycosides. Suitable monosaccharides can be in the L- or D-configuration and typically have 5, 6, or 7 carbons. Suitable monosaccharides include allose, apiose, arabinose, fructose, fucitol, fucose, galactose, glucose, glucuronic acid, mannose, A-acetylglucosamine, rhamnose, or xylose. Uridine diphosphate glycosyl transferases can catalyze formation of either an alpha or beta glycosidic bond.

Disclosed are compounds for the induction of antigen-specific immune tolerance in a subject, the compounds comprising an antigen, a polymeric linker and a liver targeting moiety, wherein the polymeric linker comprises a terminal end unit lacking each of a dithioester and a dithiobenzoate and wherein the terminal end unit confers improved stability to the compound when in solution.

The present invention relates to conjugates of amphotericin B and gold nanoparticles stabilized with thiohexoses or thiopentoses, and a method to produce said nanoparticles. As the conjugates of amphotericin B to the stabilized gold nanoparticles show several advantages over amphotericin B alone, the present invention is also directed to pharmaceutical compositions comprising said nanoparticles, and to their use for treat fungal and leishmanial infection. These amphotericin B stabilized gold nanoparticles are dispersible in water and are not toxic for mammalian cells differently from free amphotericin B and other currently used amphotericin B preparations. Importantly, the conjugates of amphotericin B and stabilized gold nanoparticles are more efficacious in treating all forms of Cryptococcal infections (planktonic, intracellular and biofilms) than amphotericin B. Additionally, the conjugates are more effective against extracellular and intracellular forms of Leishmania mexicana and Leishmania major. Therefore, amphotericin B conjugated to thiohexose or thiopentose stabilized gold nanoparticles offer safer and better treatment option than free amphotericin B, and in particular for Cryptococcal and Leishmanial infections.