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.

The present invention relates to a nucleic acid sequence comprising a nucleotide of interest and a tryptophan RNA-binding attenuation protein (TRAP) binding site, and optionally a Kozak sequence, wherein said TRAP binding site overlaps the Kozak sequence and/or the ATG start codon of the nucleotide of interest. The present invention further relates to a nucleic acid sequence comprising a nucleotide of interest and a Kozak sequence, wherein said Kozak sequence comprises a portion of a tryptophan RNA-binding attenuation protein (TRAP) binding site. The present invention further relates to a nucleic acid sequence comprising a nucleotide of interest and TRAP binding site wherein the TRAP binding site comprises a portion of the start codon ATG of said nucleotide of interest or wherein the ATG start codon comprises a portion of the TRAP binding site. The present invention further relates to a nucleic acid sequence comprising a nucleotide of interest, a binding site for tryptophan RNA-binding attenuation protein (TRAP), a multiple cloning site and a Kozak sequence, wherein said multiple cloning site is overlapping with or located downstream to the 3′ KAGN2-3 repeat of the TRAP binding site and upstream of the Kozak sequence.

Described herein are compositions and methods for modifying eukaryotic cells, for example, to express a transgene of interest and/or to produce an expanded population of cells ex vivo. Using the compositions and methods of the disclosure, a population of eukaryotic cells, such as a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) may be transduced to express a gene of interest by contacting the cells with a viral vector, such as a lentiviral vector, and a poloxamer. Additionally, the compositions and methods described herein can be used to promote the proliferation or survival of a population of pluripotent cells (e.g., CD34+ hematopoietic stem or progenitor cells) ex vivo, for example, by contacting the cells with a poloxamer. Examples of poloxamers that may be used in conjunction with the compositions and methods of the disclosure are those having a molar mass in excess of 10,000 g/mol, as well as those having a molar mass of polyoxypropylene subunits greater than 2,000 g/mol and/or an ethylene oxide content of greater than 40% by mass.

Use of 2-pentanone and specific receptor thereof in a manufacture of a product regulating a cell function, a regulation of cell function, a manufacture of a product promoting an increase in an intracellular calcium ion concentration, or a manufacture of a product promoting an increase in a neuronal firing rate is provided. In the present disclosure, the specific receptor of 2-pentanone is expressed in cultured cells or animals, and its specific binding to 2-pentanone opens ligand-gated cation channels, resulting in an increase of intracellular calcium ion concentration, depolarization of cell membranes, and generation of electrical activity or endocrine activity, thereby finally achieving precise regulation of tissue cells and organ functions. After being treated, cells can be activated rapidly, producing effects with a rapid onset; once the treatment is stopped, the experimental effect can be quickly terminated to allow the cells to return to their original state quickly.

The present invention includes compositions and methods for expanding T cells utilizing artificial antigen presenting cells (aAPCs) comprising a chimeric receptor molecule specific for CD3.

Embodiments described herein relate to compositions including genetically modified CAR cells and uses thereof for treating cancer. Some embodiments of the present disclosure relate to compositions and methods for T cell response enhancement and/or CAR cell preparation. For example, a method may include obtaining cells comprising a CAR and culturing the cells in the presence of an agent that is recognized by the extracellular domain of the CAR.

Various methods and compositions for treating age-associated conditions and other medical conditions, such as muscle diseases, type 2 diabetes, and/or obesity are described. Methods of enhancing cellular uptake of NMN and stimulating NAD+ production are further described. Various mammalian cells and mammalian cell lines are described including those comprising a cDNA encoding a Slc12a8 protein. Gene therapy vectors comprising a nucleic acid encoding Slc12a8 and non-human animals comprising an inactivating mutation in a Slc12a8 gene are also disclosed. Also described are methods for screening a candidate compound to identify compounds that promote NMN transport.

The present invention contemplates that complement receptor 1 and 2 may play a role in the induction of regulatory B cells under inflammatory conditions that accompany immune-mediated diseases. For example, long noncoding RNA may regulation transcription of the complement receptor I gene, thereby resulting in an induction and/or suppression of regulatory B cells. Such long noncoding RNA in mature B cells may be specifically targeted to modify complement receptor 1 levels and induce or suppress the generation of antigen-specific regulatory B cells, thereby modifying the course of immune mediated diseases including, but not limited to, autoimmune disease, cancer, and infection.

The present disclosure relates to methods for producing lentiviral vectors using mammalian cells. Specifically, the methods utilize three plasmids, rather than four, to provide the required packaging elements and transfer vector to a cell, allowing for the production of a large number of lentiviral vectors in mammalian cells, including suspension-based cells. These methods allow for the production of lentiviral vectors that can be tailored to include a specific gene of interest.

Disclosed are a natural killer (NK) cell expressing an anti-cotinine chimeric antigen receptor (CAR) specifically binding to cotinine, and a cell therapeutic agent containing the NK cell. The CAR-expressing NK cell which specifically binds cotinine, can effectively move to tumor tissue, regardless of the kind of cancer, depending on the binding substance bound to cotinine. Therefore, the natural killer cell can be usefully employed as a gene therapy exhibiting a highly efficient anticancer effect.