The invention provides methods and compositions relating to molecular targets identified as being capable of increasing or decreasing thermogenic potential in cells, including preadipocytes. Included in the invention are methods and compositions relating to inhibiting or suppressing the activity of an uncoupling protein 1 (UCP1) negative regulator, such as cardiac actin 1 (ACTC1), somatostatin receptor 1 (SSTR1), FAT atypical cadherin 1 (FAT1), and protein tyrosine phosphatase receptor type B (PTPRB). Also included in the invention are methods and compositions relating to activating a UCP1 positive regulator, such as phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 1 (PREX1), cortactin binding protein 2 (CTTNBP2), doublesex and mab-3-related transcription factor-like family A1 (DMRTA1), and endothelin receptor type B (ENDRB). The invention also provides methods and compositions relating to enrichment of cells having thermogenic potential based on cell surface markers, e.g., CD29, identified as being predictive of such.

Mitochondria modified by a targeting protein, according to one embodiment of the present invention, can be effectively delivered to a target. In addition, when a protein of interest bound to the modified mitochondria is delivered into a cell, various activities can be exhibited. The modified mitochondria can effectively cause cancer tissue death, and thus can also be used as an anticancer agent. Furthermore, various activities are exhibited according to a protein of interest loaded on modified mitochondria, and thus the modified mitochondria can be applied in the treatment of various diseases. Additionally, a fusion protein comprising a protein of interest and a fusion protein comprising a targeting protein, according to one embodiment of the present invention, can be used in order to modify mitochondria. Moreover, mitochondria modified with the fusion proteins exhibits various effects in a target cell.

Disclosed are compositions and methods for targeted treatment of glioblastoma multiforme (GBM). In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill Glioblastoma Stem Cells (GSCs). Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with Glioblastoma Stem Cells (GSCs) that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Provided herein is a fusion protein comprising, or alternatively consisting essentially of, or yet further consisting of an optional signal peptide, a serum albumin, an optional linker, a Phosphatase and Tensin Homolog (PTEN), and an optional purification or detectable marker in any order. Relating polynucleotides, vectors, host cells, pharmaceutical compositions and kits are also disclosed. Further provided are methods for delivering a fusion protein to a subject, treating a cancer or tumor, and/or producing the fusion protein.

The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, and wherein each of the first and second CARs is an activating CAR comprising an activating endodomain.

The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, wherein the spacer of the first CAR is different to the spacer of the second CAR and wherein one of the first or second CARs is an activating CAR comprising an activating endodomain and the other CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain.

Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

Described are compositions and methods relating to modified yeast that over-express protein phosphatases associated with the HOG pathway. The yeast produces an increased amount of ethanol and deceased amount of glycerol compared to parental cells. Such yeast is particularly useful for large-scale ethanol production from starch substrates.

The invention discloses immunoglobulin fusion proteins designed to bind both CD47 and a tumor cell antigen. The immunoglobulin fusion proteins include a SIRPα moiety that binds CD47 and an antigen binding site for a tumor cell antigen.

Provided herein are compositions, systems, kits, and methods for treating nervous system injuries caused by trauma or neurodegeneration or aging in a subject by administering a CSPG or SOCS3 reduction peptide (CRP and SRP respectively), or a nucleic acid sequence encoding the CRP or SRP, wherein both the CRP and SRP comprise a cell membrane penetrating domain, and a lysosome targeting domain, and the CRP further comprises a chondroitin sulfate proteoglycan (CSPG) binding domain, and the SRP further comprises a suppressor of cytokine signaling-3 (SOCS3) binding domain.