In one aspect, the present disclosure relates to a masked fluorogenic compound comprising a small molecule protecting group that can be cleaved following a reaction with a biomarker. In some embodiments, cleavage of the small molecule protecting group provides a fluorogenic ligand that binds to an aptamer, leading to fluorescence emission. In another aspect, the present disclosure relates to a method of detecting a disease or a disorder in a subject and/or in a biological sample from the subject.

Provided herein are compounds, compounds including traceless linkers, protein conjugates thereof, and compositions thereof. Also provided herein are methods for the treatment of diseases, disorders, and conditions, and/or the management of the symptoms thereof, associated with inflammatory diseases and autoimmune disorders further associated with the glucocorticoid receptor, glucocorticoid binding, and/or glucocorticoid receptor signalling, including administration of the compounds or payloads via traceless linker-payloads, and protein conjugates thereof.

An antibody-drug conjugate (ADC) has a structure represented by Formula (I): a pharmaceutically acceptable salt thereof wherein Ab is an antibody without glycans (i.e., the protein portion an antibody); G.sub.1 and G.sub.2 are glycan moieties, which may be the same or different; C.sub.n1 and C.sub.n2 are conjugation moieties, which may be the same or different; L.sub.1 and L.sub.2 are linker moieties, which may be the same or different; D.sub.1 and D.sub.2; are drug units which may be the same or different; and x and y are independently an integer from 0 to 8, provided that x+y≠0.

Provided herein are cell penetrating conjugates. The conjugates include non-cell penetrating proteins connected through a phosphorothioate nucleic acid, wherein the phosphorothioate nucleic acid enhances intracellular delivery of the non-cell penetrating proteins. Also provided are methods and kits including the conjugates provided herein.

The present disclosure provides a siRNA for inhibiting the expression of apolipoprotein C3 (ApoC3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA; wherein each nucleotide in the siRNA is independently a modified nucleotide, and the siRNA comprises a sense strand and an antisense strand; the sense strand comprises a nucleotide sequence A, the nucleotide sequence A having the same length as the nucleotide sequence as represented by SEQ ID NO:1 with no more than 3 nucleotide differences; the antisense strand comprises a nucleotide sequence B, the nucleotide sequence B having the same length as the nucleotide sequence as represented by SEQ ID NO:2 with no more than 3 nucleotide differences.

The present invention is directed to the field of RNA formulation, in particular to lyophilization of RNA. The invention provides a method for lyophilization of RNA. The present invention further concerns a lyophilized composition obtainable by the inventive method, a pharmaceutical composition, a vaccine and a kit or kit of parts. Moreover, the present invention provides a novel use of a lyoprotectant for lyophilizing RNA, the use of the inventive method in the manufacture of a medicament as well as the first and second medical use of the composition obtainable by the inventive method, the pharmaceutical composition, the vaccine or the kit or kit of parts according to the invention.

Disclosed herein are compounds including a nucleic acid (A), their preparation, and their use.

The present disclosure provides a class of compounds including a ligand moiety that specifically binds to a cell surface receptor, such as a mannose-6-phosphate receptor (M6PR) or a cell surface asialoglycoprotein receptor (ASGPR). The cell surface M6PR or ASGPR binding compounds can trigger the receptor to internalize into the cell abound compound. The ligand moieties of this disclosure can be linked to a variety of moieties of interest without impacting the specific binding to, and function of, the cell surface receptor, e.g., M6PR or ASGPR. Also provided are compounds that are conjugates of the ligand moieties linked to a biomolecule, such as an antibody, which conjugates can harness cellular pathways to remove specific proteins of interest from the cell surface or from the extracellular milieu. Also provided are methods of using the conjugates to target a polypeptide of interest for sequestration and/or lysosomal degradation.

The present disclosure relates generally to compositions of synthetic bifunctional molecules comprising a first domain that specifically binds to a target ribonucleic acid and a second domain that specifically binds to a target polypeptide, and uses thereof.

Glycotargeting therapeutics are useful in the treatment of transplant rejection, autoimmune disease, food allergy, and immune response against a therapeutic agent.