Abstract: Provided herein are recombinant microorganisms that express a subject polypeptide. Microorganisms can comprise an expression construct comprising a flagellin promoter operatively linked with a heterologous nucleotide sequence encoding the subject polypeptide. The flagellin promoter sequence can comprise a genetic modification that reduces CsrA inhibition of translation. Microorganisms also can comprise a genetic modification that reduces FlgM inhibition of SigD initiation of transcription. The target polypeptide can be an aldehyde dehydrogenase. Such microorganisms are useful in the treatment of alcohol hangover.

Abstract: Compounds that either produced a higher proportion or greater absolute number of phenotypically identified naive, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies with improved efficacy are provided.

Abstract: Understanding the complex effects of genetic perturbations on cellular state and fitness in human pluripotent stem cells (hPSCs) has been challenging using traditional pooled screening techniques which typically rely on unidimensional phenotypic readouts. Here, Applicants use barcoded open reading frame (ORF) overexpression libraries with a coupled single-cell RNA sequencing (scRNA-seq) and fitness screening approach, a technique we call SEUSS (ScalablE fUnctional Screening by Sequencing), to establish a comprehensive assaying platform. Using this system, Applicants perturbed hPSCs with a library of developmentally critical transcription factors (TFs), and assayed the impact of TF overexpression on fitness and transcriptomic cell state across multiple media conditions. Applicants further leveraged the versatility of the ORF library approach to systematically assay mutant gene libraries and also whole gene families.

Abstract: The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices.

Abstract: Compositions and methods are provided for treating ocular neuropathy in a subject. In one aspect, a recombinant adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding NRF2. In another aspect, a recombinant adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding SIRT1. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.

Abstract: A therapeutic agent comprising a nucleic acid and a TCR modified immune cell and use thereof. The therapeutic agent comprises a first composition comprising a first active ingredient and a second composition comprising a second active ingredient. The first active ingredient includes or contains a nucleic acid having a labeling polypeptide coding sequence for being introduced into a tumor cell and/or a cancer cell. The labeling polypeptide has one or more epitope polypeptides which can be presented on a surface of the tumor cell and/or cancer cell by MHC class I molecules. The second composition comprises a second active ingredient in a second pharmaceutically acceptable carrier and the second active ingredient comprises a T cell receptor modified immune cell which can specifically recognize and bind to the epitope polypeptide presented by MHC class I molecules. The therapeutic agent achieves synergistic treatment effect and provides a new route for tumor treatment.

Abstract: Livestock animals and progeny thereof comprising at least one edited chromosomal sequence that alters expression or activity of a somatostatin receptor (SSTR) protein are provided. Livestock animal cells that contain such edited chromosomal sequences are also provided. The livestock animals have improved growth performance and weight gain. Methods for producing livestock animals with increased growth performance are also provided.

Abstract: A therapeutic agent and method of administering the therapeutic agent for the treatment of tumors and/or cancers of a subject, the therapeutic agent comprising a first pharmaceutical composition comprising a first active ingredient in a first druggable vehicle, wherein the first active ingredient comprises a nucleic acid encoding a labelling polypeptide comprising one or more antigenic epitope peptides and/or encoding a MHC protein; a second pharmaceutical composition comprising a second active ingredient in a second druggable vehicle, wherein the second active ingredient comprises immune cells purified from peripheral blood or from tumor tissue and are cultured in vitro; wherein the nucleic acid when administered to the subject as part of the pharmaceutical composition causes the tumor cells and/or cancer cells of the subject to express the one or more antigenic epitope peptides to elicit an immune response of the immune cells.

Abstract: The invention provides expression vectors, nucleic acids, vector particles and methods of treatment involving these vector particles, comprising an engineered KCNA1 gene encoding an edited Kv1.1 potassium channel, as well as methods of confirming the presence of engineered KCNA1 mRNA in a cell. The features of the engineered KCNA1 gene combine to advantageously enhance the translation and activity of the Kv1.1 protein and improve detection of KCNA1 gene expression in a cell and can be used for example in the treatment of epilepsy and similar neurological disorders.

Abstract: A perfusion plate that can be combined with pillar plates containing cell layers is disclosed. The perfusion plate can have an inflow reservoir and an outflow reservoir connected by at least one channel, which fluidly connects the perfusion wells to the reservoirs for the flow of a fluid such as growth media. A perfusion plate can be part of an assembly containing a pillar plate, a lid, and a transparent bottom for visualizing cell growth in the perfusion wells. The perfusion-pillar plate assembly can facilitate perfusion-based tissue culture and tissue communication for high throughput, high-content, drug screening.

Abstract: Provided herein are, inter alia, methods useful for delivering nucleic acids and kinase inhibitors to a cell. The methods provided herein include the delivery of therapeutic nucleic acids to cancer cells by contacting a cancer cell with a kinase inhibitor and a therapeutic nucleic acid. The methods provided herein are therefore, inter alia, useful for the treatment of cancer.

Abstract: The present invention relates to a cell line, use of the cell line and a method for producing infectious viral particles using said cell line.