The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

Oligonucleotides are provided herein that inhibit PLP1 expression. Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders and/or conditions associated with PLP1 expression.

Compounds, compositions and methods for reducing off-target toxicity of T cells expressing a chimeric antigen receptor (CAR-T cells) and/or providing enhanced control of CAR-T cell activation, and methods of treating a subject and/or modifying CAR-T cell activity in a subject with cancer.

An siRNA conjugate having a structure as represented by formula (1) for inhibiting hepatitis B vims gene expression, comprising siRNA and a conjugated group, wherein the sense strand of the siRNA comprises a nucleotide sequence 1, and the antisense strand comprises a nucleotide sequence 2; the nucleotide sequence 1 and the nucleotide sequence 2 are, at least in part, reversely complementary to form a double-stranded region; the nucleotide sequence 1 and SEQ ID NO: 1 are equal in length and differ by no more than three nucleotides; the nucleotide sequence 2 and SEQ ID NO: 2 are equal in length and differ by no more than three nucleotides. The siRNA conjugate can specifically target liver cells and effectively solve the problem of siRNA delivery in vivo, and shows excellent activity and low toxicity to inhibit HBV gene expression while maintaining high stability of siRNA.

The present invention relates to nucleic acids, double stranded nucleic acids (dsNAs), and agents for inhibiting expression of STATS. The present invention also includes nanoparticles comprising the nucleic acids, the dsNAs, and/or the agents as well as methods of treating cancer using the nucleic acids, the double stranded nucleic acids (dsNAs), the agents and/or the nanoparticles as disclosed herein. In one embodiment, the target region is within the 3-UTR region of STATS mRNA.

Disclosed are proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of c-MYC protein. The disclosed PROTACs typically include a first targeting moiety that binds to c-MYC (M.sub.c-MYC) which may be derived from a substituted heterocycle that binds to c-MYC such as a substituted pyrazole. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (M.sub.E3). As such, the disclosed PROTACS may be described as having a formula M.sub.c-MYC-L-M.sub.E3 or M.sub.E3-L-M.sub.c-MYC.

Disclosed are compounds for the selective labeling of cell-surface sugars in cancer cells. The compounds are activatable by triggers specific to cancer cells, and, when metabolized, label a cancer cell surface sugar with an azide chemical group. Facilitated by a click chemistry reaction, combination of the cell surface-expressed azide with a alkynyl-drug conjugate enables efficient targeted drug delivery to cancer cells with reduced toxicity. Also disclosed are compounds for delivering a drug to an azide-bearing cancer cell, and methods of treating cancer using the compounds.

The present invention provides the modular design and assembly of novel targeting bio-conjugates, exclusively assembled by means of biotin-biotin binding element conjugation, comprising mono-biotinylated cell binding component, a tetrameric biotin-binding element, and mono-biotinylated payload for therapeutic and diagnostic purposes. In addition, there is provided a method of delivering the payload, such as therapeutic oligonucleotides, via mono-biotinylated targeting devices, such as antibodies or ligands, into eukaryotic cells by means of receptor-mediated endocytosis. The targeting bio-conjugates are suitable for use in the areas of medicine, pharmacy and biomedical research.

Compositions of a modulator of cell metabolism, typically targeting cellular glycolysis, preferably with a targeting moiety, attached directly or indirectly to the inhibitor, or to a nanoparticle or other delivery vehicle thereof, and methods of use for treating cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases are provided. Pharmaceutical compositions including the targeted modulator and a pharmaceutically acceptable carrier are also provided. The pharmaceutical compositions can be administered to a subject in need thereof in an effective amount to reduce one or symptoms of the cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases alone or prior to or in conjunction with a further therapy such as radiotherapy.

A conjugate comprising a pyrrole-imidazole polyamide that recognizes a specific DNA sequence and a bromodomain inhibitor, a composition for regulating biochemical activity, specifically for regulating histone modification, e.g., for inducing histone acetylation, which comprises the conjugate, a composition for recruiting a bromodomain-containing protein which comprises the conjugate, a method for nucleosome acetylation which comprises using the conjugate, and a method for bromodomain-containing protein recruitment which comprises using the conjugate are provided.