The invention provides an improved host strain for production of desired protein.

Disclosed is a dTAG system comprising small molecule degraders of mutant BET family protein-tagged proteins via recruitment of an E3 ubiquitin ligase and uses thereof.

Degradation compounds include a cyclic cell penetrating peptide (cCPP) and a degradation construct. The degradation construct includes a degradation moiety and a targeting moiety. The targeting moiety binds a target protein. When the targeting moiety is bound to the target protein, the degradation moiety mediates degradation of the target protein. The cCPP facilitates transfer of the degradation construct into a cell. The degradation compound may further include an exocyclic peptide to enhance endosomal escape of the compound or degradation construct once inside the cell.

Methods of assessing the efficacy of an agent in treating a disease or disorder are provided that include determining whether the agent causes, or inhibits, direct or indirect recruitment and/or ubiquitination and/or degradation of argininosuccinate synthetase 1 (ASS1).

Described herein are agents that inhibit CBL autoinhibition, agents that activate CBL, SLAP and/or SLAP2 mimetics, and recombinant SLAP and/or SLAP2 or variants and/or fragments thereof that inhibit CBL autoinhibition. Also described are fusion proteins comprising these molecules as well as methods of inhibiting CBL autoinhibition and related uses thereof.

Disclosed herein is a method of treating a cancer in a subject having or suspected of having the cancer that has a mutated PREX2 expressed thereon. According to the embodiment of the present disclosure, the mutation is G258V, S1113R, E1346D or K400fs. The method includes the step of administering an effective amount of a composition to the subject, wherein the composition includes a therapeutic molecule for producing a polypeptide that exhibits a binding affinity to the mutated PREX2 protein expressed in the cancer in the subject.

Angelman Syndrome (AS) is a genetic disorder occurring in approximately one in every 15,000 births. It is characterized by severe mental retardation, seizures, difficulty speaking and ataxia. The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase. A unique feature of this gene is that it undergoes maternal imprinting in a neuron-specific manner. In the majority of AS cases, there is a mutation or deletion in the maternally inherited UBE3A gene, although other cases are the result of uniparental disomy or mismethylation of the maternal gene. While most human disorders characterized by severe mental retardation involve abnormalities in brain structure, no gross anatomical changes are associated with AS. We have generated a Ube3a protein with additional sequences that should allow the secretion from cells and uptake by neighboring neuronal cells. This would confer a functional E6-AP protein into the neurons and rescue disease pathology.

The disclosure provides gene therapy vectors, such as adeno-associated virus (AAV), designed for treatment of an Interferon regulatory factor 2 binding protein like (IRF2BPL) disorder.

An auxin-inducible degron system kit that controls degradation of a target protein in a non-plant-derived eukaryotic cell, the kit containing a first nucleic acid that encodes a mutant TIR1 family protein having a mutation at an auxin-binding site, an auxin analog that has an affinity to the mutant TIR1 family protein and a second nucleic acid that encodes a degradation tag containing at least a part of an Aux/IAA family protein and having an affinity to a complex of the mutant TIR1 family protein and the auxin analog.

The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.