The present disclosure relates generally to the field of immunotherapy. In particular, the present disclosure describes to 20 single nucleotide variants (SNVs) within the A20 coding sequence that can differentially impact the immune system. Differential expression of the identified A20 SNVs can be used to “tune” the immune system of a subject e.g., tune up or tune down the sensitivity and/or strength of the immune system of a subject in response to a treatment or a pathogen. On the basis, the present disclosure provides methods for modulating the immune system of a subject by modulating the A20 SNV expression profile in the subject, thereby “tuning” the immune system. The present disclosure also describes reagents for use in such methods. The methods and reagents may have application in the treatment and/or management of diseases/conditions such as, for example, cancer, autoimmune disease, pathogenic infection, complement deficiency, and transplant rejection, where the strength of a subject's immune system plays an important role. The present disclosure also describes methods in which the A20 SNVs are used as biomarkers to stratify subjects according to the strength of their immune system e.g., strong or poor immune response relative to a reference A20 genotype, and the use of such methods in personalised medicine.

An antisense oligonucleotide comprising a sequence targeted to the 3′ untranslated region (3′ UTR) of the TNFAIP3 (A20) transcript and its use as a medicament, for example in the treatment of cancer or an autoimmune disease.

The invention relates to peptide inhibitors of linear ubiquitin chain assembly complex (LUBAC) and to methods of treating diseases including activated B-cell like diffuse large B cell lymphoma (ABC DLBCL) and autoimmune or inflammatory disorders.

USP14 is a biomarker for recurrent disease and inhibition of USP14 is of therapeutic benefit for women with endometrial or ovarian cancer.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Provided is a method for preventing or treating a metabolic disorder, including administering to a subject a therapeutically effective amount of TRABID protein or a functionally related variant thereof, or a nucleic acid encoding TRABID protein or a functionally related variant thereof. Also provided is a method for reducing fat accumulation through TRABID-induced deubiquitination to promote autophagy activity and lipid metabolism.

Survival-targeting chimeric (SURTAC) molecules are provided herein, as well as methods for their use in removing ubiquitin molecules from ubiquitinylated proteins. In one embodiment, the SURTAC molecule comprises a first binding domain, a second binding domain, and a linker domain, wherein the first binding domain is configured to bind to an ubiquitinylated protein; the second binding domain is configured to bind to an ubiquitin protease that cleaves one or more ubiquitin from the ubiquitinylated protein bound to the first binding domain, and the linker domain is configured to link the first binding domain to the second binding domain.

The invention relates to methods for increasing plant yield, and in particular grain yield by reducing or abolishing the expression and/or activity of OTUB1 in a plant. Also described are genetically altered plants characterised by the above phenotype and methods of producing such plants.

Compositions and methods for treating cancer are provided. In accordance with the instant invention, methods of inhibiting or treating cancer, particularly a “cold” cancer or a cancer lacking CD8+ tumor infiltrating lymphocytes (TILs) and/or other immunostimulatory features, in a subject are provided. In a particular embodiment, the method comprises administering an agent which increases ubiquitin-specific protease 6 (USP6) activity and/or expression to the subject.

The present invention relates to a ubiquitin-specific peptidase 24 inhibitor, a medicinal composition including the same and a method of delaying or reversing multidrug resistance in cancers using the same. The USP24 inhibitor, which includes a shUSP24 RNA and/or a carbonyl substituted phenyl compound, can serve as a chemosensitizing agent for inhibiting the drug pump out, cancer sternness and genomic instability of cancer cells, thereby being applied to a medicinal composition and a method for delaying or reversing multidrug resistance in cancers.