Abstract: Disclosed are compositions and methods related to the construction and use of conditional universal synthetic notch (synNotch) receptors and conditional chimeric antigen receptor (CAR) T cells. Also disclosed herein are methods of using said synNotch receptors in the construction of engineered cells. It is contemplated herein that the disclosed synNotch receptors and engineered cells can be used in regenerative medicine. Additionally disclosed herein are methods of using the disclosed synNotch, CAR T cells, and engineered cells in the treatment of cancer, autoimmune disease, autoinflammatory disease, and infectious disease.

Abstract: A compound, or a pharmaceutically acceptable salt thereof, having a structure of: wherein L is a cleavable linker group; X is a cargo moiety-containing group; and R1 and R2 are each independently hydrogen, alkyl, or substituted alkyl; or R1 and R2 together form a boronic ester ring or a substituted boronic ester group.

Abstract: Disclosed are compositions and methods related to the construction and use of universal synthetic notch (synNotch) receptors and chimeric antigen receptor (CAR) T cells.

Abstract: Provided herein are small molecule compounds and methods inhibiting human sulfotransferase 1A3 (SULT1A3) using these small molecule compounds. Methods of manufacturing and treatment are also disclosed.

Abstract: Disclosed herein is a genetically encoded light- or chemically-activated Cas9 engineered through the site-specific installation of an activatable lysine amino acid. Such activatable Cas9 proteins can be used in CRISPR/Cas9 systems to control gene expression temporally, spatially, or both. Systems, methods, kits, and compositions for manipulation of sequences and/or activities of target sequences are provided. Also provided are methods of directing CRISPR complex formation in cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas9 system.

Abstract: A compound, or a pharmaceutically acceptable salt thereof, having a structure of: wherein L is a cleavable linker group; X is a cargo moiety-containing group; and R1 and R2 are each independently hydrogen, alkyl, or substituted alkyl; or R1 and R2 together form a boronic ester ring or a substituted boronic ester group.

Abstract: The invention relates to a polypeptide comprising an amino acid having a norbornene group. Suitably said norbornene group is present as an amino acid residue of a norbornene lysine. The invention also relates to a method of producing a polypeptide comprising a norbornene group, said method comprising genetically incorporating an amino acid comprising a norbornene group into a polypeptide.

Abstract: Disclosed herein is a genetically encoded light- or chemically-activated Cas9 engineered through the site-specific installation of an activatable lysine amino acid. Such activatable Cas9 proteins can be used in CRISPR/Cas9 systems to control gene expression temporally, spatially, or both. Systems, methods, kits, and compositions for manipulation of sequences and/or activities of target sequences are provided. Also provided are methods of directing CRISPR complex formation in cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas9 system.

Abstract: The invention relates to a method of making a polypeptide comprising an orthogonal functional group, said orthogonal functional group being comprised by an aliphatic amino acid or amino acid derivative, said method comprising providing a host cell; providing a nucleic acid encoding the polypeptide of interest; providing a tRNA-tRNA synthetase pair orthogonal to said host cell; adding an amino acid or amino acid derivative comprising the orthogonal functional group of interest, wherein said amino acid or amino acid derivative is a substrate for said orthogonal tRNA synthetase, wherein said amino acid or amino acid derivative has an aliphatic carbon backbone; and incubating to allow incorporation of said amino acid or amino acid derivative into the polypeptide of interest via the orthogonal tRNA-tRNA synthetase pair. The invention also relates to certain amino acids, and to polypeptides comprising same.

Abstract: This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Abstract: The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetase that can incorporate unnatural amino acid into proteins produced in eubacterial host cells such as E. coli, or in a eukaryotic host such as a yeast cell. The invention provides, for example but not limited to, novel orthogonal synthetases, methods for identifying and making the novel synthetases, methods for producing proteins containing unnatural amino acids, and translation systems.

Abstract: This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Abstract: The invention relates to a polypeptide comprising an amino acid having a norbornene group. Suitably said norbornene group is present as an amino acid residue of a norbornene lysine. The invention also relates to a method of producing a polypeptide comprising a norbornene group, said method comprising genetically incorporating an amino acid comprising a norbornene group into a polypeptide. The polypeptide comprising the norbornene group can be specifically labelled by inverse electron demand Diels-Alder reaction with a tetrazine compound.

Abstract: The present invention is a method for identifying agents which modulate microRNA activity. The invention involves contacting a cell harboring a microRNA and a microRNA binding sequence, which is operably linked to a nucleic acid molecule encoding a reporter protein, with a test agent and determining whether the test agent increases or decreases the expression of the reporter protein thereby identifying a microRNA modulator. Antagonists identified by this screening assay are provided, as are methods for using the same to inhibit microRNA activity and prevent or treat disease.

Abstract: This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Abstract: The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetase that can incorporate unnatural amino acid into proteins produced in eubacterial host cells such as E. coli, or in a eukaryotic host such as a yeast cell. The invention provides, for example but not limited to, novel orthogonal synthetases, methods for identifying and making the novel synthetases, methods for producing proteins containing unnatural amino acids, and translation systems.

Abstract: This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Abstract: The present invention is a method for identifying agents which modulate microRNA activity. The invention involves contacting a cell harboring a microRNA and a microRNA binding sequence, which is operably linked to a nucleic acid molecule encoding a reporter protein, with a test agent and determining whether the test agent increases or decreases the expression of the reporter protein thereby identifying a microRNA modulator. Antagonists identified by this screening assay are provided, as are methods for using the same to inhibit microRNA activity and prevent or treat disease.

Abstract: MicroRNAs are a class of endogenous regulators of gene function. Aberrant regulation of microRNAs has been linked to various human diseases, most importantly cancer. Small molecule intervention of microRNA misregulation has the potential to provide new therapeutic approaches to such diseases. microRNA miR-122 is the most abundant microRNA in the liver and is involved in hepatocellular carcinoma development and hepatitis C virus (HCV) infection. Small molecule inhibitors and activators of the microRNA miR-122 are described, and methods for their identification are reported. These small molecule inhibitors reduce viral replication in liver cells and thus represent a new approach to the treatment of HCV infections. Moreover, small molecule activation of miR-122 in liver cancer cells selectively induced apoptosis through caspase activation, and thus has implications in cancer chemotherapy.

Abstract: The present invention is a method for identifying agents which modulate microRNA activity. The invention involves contacting a cell harboring a microRNA and a microRNA binding sequence, which is operably linked to a nucleic acid molecule encoding a reporter protein, with a test agent increases or decreases the expression of the reporter protein thereby identifying a microRNA modulator. Antagonists identified by this screening assay are provided, as are methods for using the same to inhibit microRNA activity and prevent or treat disease.