The present disclosure refers to an endonuclease-based gene editing construct, wherein the construct comprises a CRISPR-associated endonuclease (such as Cas9 or Cpf1) or a derivative thereof and at least one or more hormone binding domains of the estrogen receptor (ERT2) or derivatives thereof. The present disclosure also describes a method of editing a genome of a host cell using the construct as disclosed herein, the method comprising transfecting the host cell with the nucleic acid sequence as defined herein and incubating the cell with an inducing agent.

The disclosure is directed to a G-protein coupled receptor complex. The complex includes (i) a chimeric G protein-coupled receptor (GPCR) comprising a non-native amino acid sequence located within the C-terminus of the GPCR and a synthetic phosphopeptide ligated to the non-native amino acid sequence; and (ii) a ?-arrestin (?arr) protein bound to the C-terminus of the GPCR. The disclosure also provides an in vitro method for producing the aforementioned complex, as well as methods for identifying compounds or ligands which bind to and modulate the activity of the complex. Positive allosteric modulators of the ?2 adrenergic receptor identified by screening a DNA-encoded library potentiate the activity of ?2 agonists and have application in the treatment of obstructive airway disease, bronchospasm, or pre-term labor.

The present disclosure provides recombinant T cells that include a vector encoding one or more of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC1?), mitochondrial transcription factor A (Tfam), GA binding protein transcription factor alpha subunit (GABPA), and estrogen-related receptor alpha (ERR? ). Such recombinant T cells can also include a chimeric antigen receptor (CAR) or a recombinant T cell receptor (TCR). Methods of using these recombinant T cells in cancer immunotherapy are provided. Also provided are kits and compositions that can be used with such methods.

Described herein is the finding that increasing the frequency of Zscan4 activation in mouse ES cells not only enhances, but also maintains their developmental potency in long-term cell culture. As the potency increases, even a whole animal can be produced from a single ES cell injected into a 4N blastocyst at an unexpectedly high success rate. The studies disclosed herein indicate that ES cells acquire higher potency by going through the transient Zscan4 activation state more frequently than the regular state. Particularly disclosed herein is the finding that the constitutive presence of Zscan4-ERT2, even in the absence of its usual activator tamoxifen, can increase the frequency of endogenous Zscan4 activation in ES cells, resulting in the increase of developmental potency of the ES cells. Accordingly, provided herein are Zscan4-ERT2 fusion proteins and nucleic acid molecules and vectors encoding Zscan4-ERT2 fusion proteins. Further provided are methods of prolonging and/or enhancing stem cell pluripotency using the disclosed Zscan4-ERT2 nucleic acid molecules and fusion proteins.

The present disclosure relates to methods of determining a treatment course of action. In particular, the present disclosure relates to mutations in the gene encoding estrogen receptor and their association with responsiveness to estrogen therapies for cancer.

The present invention relates to genetically modified HepaRG cells as deposited on Oct. 5, 2016 at the Leibniz-Institut DSMZ Deutsche Sammlung von Mikroorganismen and Zellkulturen GmbH, under No. DSM ACC3291. The invention further relates to methods of culturing said cells and cell cultures comprising said cells. The invention further relates to uses of the genetically modified HepaRG cells.

This disclosure relates to compositions and methods for treating cancer using armored chimeric antigen receptor cells.

The disclosure is directed to a G-protein coupled receptor complex. The complex includes (i) a chimeric G protein-coupled receptor (GPCR) comprising a non-native amino acid sequence located within the C-terminus of the GPCR and a synthetic phosphopeptide ligated to the non-native amino acid sequence; and (ii) a ?-arrestin (?arr) protein bound to the C-terminus of the GPCR. The disclosure also provides an in vitro method for producing the aforementioned complex, as well as methods for identifying compounds or ligands which bind to and modulate the activity of the complex. Positive allosteric modulators of the ?2 adrenergic receptor identified by screening a DNA-encoded library potentiate the activity of ?2 agonists and have application in the treatment of obstructive airway disease, bronchospasm, or pre-term labor.

The present invention discloses a method of constructing a pharmacophore to determine whether a molecule is a peroxisome proliferator-activated receptor ? full agonist, partial agonist or antagonist in terms of a binding energy or a free energy surface comprising: providing a protein receptor mimicking said peroxisome proliferator-activated receptor ? and a corresponding ligand; docking the corresponding ligand and the protein receptor to form a docked conformation; performing at least two rounds of molecular dynamic simulation to obtain at least one trajectory and at least one free energy surface; inputting the trajectory to construct at least one pharmacophore and obtaining the binding energy of the corresponding ligand; comparing the molecule with the corresponding ligand in terms of the binding energy thereof to the protein receptor in order to determine whether the molecule is the peroxisome proliferator-activated receptor ? full agonist, partial agonist or antagonist.

The compositions described herein include an epitope of a peptide that may elicit an immune response in a subject following administration. The compositions may comprise nucleic acids. The compositions may comprise peptides. The methods described herein include administering a composition comprising an epitope of a peptide to a subject in need thereof.