Abstract: The present invention relates to a human induced pluripotent stem cell line transformed with fluorescent protein-tagged CYP1A1 and an AHR modulator screening method using the same. Specifically, a human-induced pluripotent stem cell line (hiPSC line) in which a gene was edited to express a cytochrome P450 1A1 (CYP1A1) protein in a state of fusion with a fluorescent protein without inhibiting its unique function was prepared, and it was confirmed that an AHR modulator could be screened by screening cells in a living state using the cell line-derived liver cells better than in the case of using existing human primary hepatocytes (hPH) or HepG2 cells. Therefore, the CYP1A1-mCherry hiPSC cell line of the present invention can be effectively used for screening AHR modulating compounds.

Abstract: Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors. Using the described reprogramming protocol, one is able to consistently reprogram non-T cells with close to 100% success from non-T cell or non-B cell sources. Further advantages include use of a defined reprogramming media E7 and using defined clinically compatible substrate recombinant human L-521. Generation of iPSCs from these blood cell sources allows for recapitulation of the entire genomic repertoire, preservation of genomic fidelity and enhanced genomic stability.

Abstract: The present invention relates to a method for rescue of Vesicular Stomatitis Virus (VSV) from DNA in a HEK293 cell line or a HEK293 cell line adapted to suspension growth comprising (a) providing cells from a HEK293 cell line or a HEK293 cell line adapted to suspension growth in cell culture, (b) transfecting the cells with at least one plasmid, wherein the at least one plasmid comprises (i) an expression cassette comprising a VSV genomic cDNA; (ii) at least one expression cassette encoding VSV nucleoprotein (N) protein, VSV phosphoprotein (P) protein, and VSV large (L) protein; and (iii) an expression cassette encoding SV40 Large T antigen; (c) culturing the transfected cells; and (d) harvesting the cell culture supernatant comprising the rescued VSV.

Abstract: This disclosure describes a method that includes using dorsomorphin to increase the infectivity of adeno-associated virus (AAV). The AAV may be of any AAV serotype. In some embodiments, dorsomorphin may be used in combination with IL-6 or TNF? or both. This disclosure further describes methods for using dorsomorphin-treated cells to determine neutralizing antibody (NAb) titers.

Abstract: Some embodiments provided herein relate to gene delivery systems and methods using a single plasmid that carries a self-inactivating transposase gene and a corresponding transposon. Some embodiments include nucleic acids having certain sequences, vector including such nucleic acids, and compositions including the vectors.

Abstract: The present disclosure provides methods for inducing cell cycle reentry of postmitotic cell. The present disclosure further provides cells and compositions for treating diseases, such as cardiovascular diseases, neural disorders, hearing loss, and diabetes.

Abstract: Compositions and methods for binding to a target sequence of interest are provided. Compositions include fusion proteins between DNA binding proteins or protein domains and nucleic acid modifying proteins or protein domains. The compositions find use in cleaving or modifying a target sequence of interest, visualization of a target sequence of interest, and modifying the expression of a sequence of interest. Compositions comprise RNA-guided nuclease polypeptides, CRISPR RNAs, trans-activating CRISPR RNAs, guide RNAs, deaminases, and nucleic acid molecules encoding the same. Vectors and host cells comprising the nucleic acid molecules are also provided. Further provided are CRISPR systems for binding a target sequence of interest, wherein the CRISPR system comprises an RNA-guided nuclease polypeptide and one or more guide RNAs. Also provided are deaminases which may be fused to a DNA-binding polypeptide and may be useful for gene editing.

Abstract: The present invention provides compositions and methods for reprogramming somatic cells using purified RNA preparations comprising single-strand mRNA encoding an iPS cell induction factor. The purified RNA preparations are preferably substantially free of RNA contaminant molecules that: i) would activate an immune response in the somatic cells, ii) would decrease expression of the single-stranded mRNA in the somatic cells, and/or iii) active RNA sensors in the somatic cells. In certain embodiments, the purified RNA preparations are substantially free of partial mRNAs, double-stranded RNAs, un-capped RNA molecules, and/or single-stranded run-on mRNAs.

Abstract: The present invention provides methods and compostions to improve the efficiency of somatic cell nuclear transfer (SCNT) and the consequent production of nuclear transfer ESC (ntESC) and transgenic cells and/or non-human animals. More specifically, the present invention relates to the discovery that trimethylation of Histone H3-Lysine 9 (H3K9me3) in reprogramming resistant regions (RRRs) in the nuclear genetic material of donor somatic cells prevents efficient somatic cell nuclear reprogramming or SCNT. The present invention provide methods and compositions to decrease H3K9me3 in methods to improve efficacy of SCNT by exogenous or overexpression of the demethylase Kdm4 family and/or inhibiting methylation of H3K9me3 by inhibiting the histone methyltransferases Suv39h1 and/or Suv39h2.

Abstract: The present invention provides chimeric cytokine receptors, particularly chimeric cytokine receptors that can be activated in tumor microenvironment, and their uses in tumor immunotherapy (e.g., adoptive cell therapy). The present invention further provides methods of genetically modifying therapeutic cells resulting in an enhanced immune response against a target antigen. The application further provides therapeutic cells that express said chimeric cytokine receptors and methods for treating patients using the modified therapeutic cells.

Abstract: The present invention relates to a method and composition for optimized intracellular delivery of nucleic acids, in particular mRNA. In addition to mRNA, the composition, in particular a nanoparticle, may include a glycolipid antigen. Combinations with checkpoint inhibitors are also provided. The method and composition of the invention targets antigen presenting cells and is especially useful for immunotherapy and vaccination purposes.

Abstract: The present invention features compositions and methods for recapitulating physiological X-chromosome inactivation (XCI) in a cell, including a cell of any embryo generated by Somatic Cell Nuclear Transfer (SCNT). In one aspect, the invention features a method for generating physiological X chromosome inactivation in an embryo generated by SCNT, the method comprising injecting the embryo generated via SCNT with an H3K27me3-specific demethylase polypeptide or a polynucleotide encoding said demethylase. Disclosed herein are methods, compositions, and kits comprising an agent which increases the expression of genes encoding an H3K27me3-specific demethylase, or increases the activity of human H3K27me3-specific demethylase.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of stem cells into Schwann cell precursors and Schwann cells, and Schwann cell precursors and Schwann cells generated by such methods. The presently disclosed subject matter also provides for uses of such Schwann cell precursors and Schwann cells for regeneration of PNS and/or CNS, for prevention and/or repair of myelin damages, and/or for prevention and/or treatment of Schwann cell related disorders (e.g., peripheral neuropathy, e.g., Diabetic Peripheral Neuropathy).

Abstract: Methods and compositions for treating diseases or disorders of the nervous system using promoter-driven Designer Receptor Exclusively Activated by Designer Drugs (DREADDs) and DREADD agonists are disclosed.

Abstract: An immunoresponsive cell, such as a T-cell expressing (i) a second generation chimeric antigen receptor comprising: (a) a signalling region; (b) a co-stimulatory signalling region; (c) a transmembrane domain; and (d) a binding element that specifically interacts with a first epitope on a target antigen; and (ii) a chimeric costimulatory receptor comprising (e) a co-stimulatory signalling region which is different to that of (b); (f) a transmembrane domain; and g) a binding element that specifically interacts with a second epitope on a target antigen. This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

Abstract: The present invention provides, among other things, improved methods and pharmaceutical compositions for treating cystic fibrosis based on codon optimized mRNA encoding an engineered or mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein.

Abstract: The current invention provides for methods and systems of inducing cell cycle exit and terminal differentiation in stem cells undergoing differentiation into various mature cell types in particular pancreatic endocrine cells. The current invention also provides for methods and systems of inducing differentiation of pancreatic endocrine cells from stem cells. The invention also provides for the cells produced by the methods that are suitable for transplantation or grafting into a subject for the prevention and/or treatment of disease, and useful for basic research and drug testing.

Abstract: 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.

Abstract: The present disclosure relates generally to ex vivo primary tumor models prepared from fresh tumor tissues which are useful for screening anti-cancer agents. The fresh tumor tissues are prepared and cultured under suitable conditions to grow an outgrowth of endothelial cells. Killing of these endothelial cells by a candidate agent indicates the efficacy of the agent in inhibiting tumor angiogenesis.

Abstract: Provided are compositions useful for treating an ophthalmological condition due to one or more loss-of-function mutations in the gene encoding the Retinol Dehydrogenase 12 (RDH12) protein. Provided herein are nucleic acids encoding a human RDH12 and vectors comprising an expressible coding region for human RDH12. Also provided are uses of such nucleic acids and vectors for treating ophthalmological disease, including, but not limited to Leber Congenital Amaurosis.