Abstract: The present disclosure provides a method of increasing the functionality of a GABAergic interneuron in the hilus of the hippocampus of an individual having at least one apolipoprotein E4 (apoE4) allele. The method generally involves reducing tau levels in the interneuron.

Abstract: Healthy functional platelets are mass produced. A method for producing platelets, comprising: (1) a culture step of culturing megakaryocytes in a platelet producing medium in the presence of mechanical stress and platelet production promoting factors including MIF, NRDc, IGFBP2, TSP-1, PAI-1, and CCL5, and (2) a harvest step of harvesting the platelets obtained by the culture step; wherein the culture step comprises: (a) a step of promoting a release of the platelet production promoting factors from megakaryocytes by mechanical stress; and/or (b) a step of externally adding platelet production promoting factors including MIF, NRDc, and IGFBP2.

Abstract: A non-human papilloma pseudovirus or virus like particle has at least one papilloma capsid protein codon-optimized for expression in eukaryotic cells or cell lines. A pharmaceutical composition includes the non-human papilloma pseudovirus or virus like particle, and a diagnostic agent, an imaging agent, and a therapeutic agent. A non-human papilloma pseudovirus or virus like particle can be used as a medicament. A method for producing a non-human papilloma pseudovirus or virus like particle involves codon-optimizing of capsid proteins of non-human papillomaviruses for expression in eukaryotic cells, synthesizing of the sequences and cloning of the synthesized sequences into expression vectors, and producing non-human papilloma pseudovirus or virus like particles. ?-carrageenan can be used as transduction enhancer for non-human papilloma pseudovirus or virus like particles in vitro.

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: Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

Abstract: A novel cell culture method for inducing differentiation of a pluripotent stem cell into trophoblast and an automatic culture apparatus therefor includes: a first step of culturing the pluripotent stem cell in a presence of a ROCK inhibitor during a first time period; a second step of culturing the pluripotent stem cell, which has been subjected to the first step, without the ROCK inhibitor during a second time period following the first time period; and a step of culturing the pluripotent stem cell, which has been subjected to the second step, in the presence of the ROCK inhibitor during a third time period following the second time period, in which the pluripotent stem cell is cultured in a state of being adhered to a cell culture substrate including a planar mesh through the first to third time periods.

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: Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

Abstract: Methods of producing non-human animal models of corneal ectatic diseases, such as corneal keratoconus, by applying an aromatic compound to the eye of a non-human animal are described. Also described are non-human animal models of corneal ectatic diseases, and methods of using the non-human animal models to screen compounds that modulate corneal ectatic diseases.

Abstract: RNA encoding immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially a neutral surface charge at physiological pH and are effective for immunisation.

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: The present invention discloses an in vitro method for the generation of a cell composition comprising or consisting of ventral midbrain dopaminergic progenitor cells from a cell composition comprising pluripotent and/or multipotent stem cells, the method comprising the steps of A) differentiating said pluripotent and/or multipotent stem cells into ventral dopaminergic progenitor cells, thereby generating a cell composition comprising ventral dopaminergic progenitor cells comprising ventral midbrain dopaminergic progenitor cells and ventral hindbrain dopaminergic progenitor cells, and B) Enriching CD117 positive cells from said cell composition comprising ventral dopaminergic progenitor cells by using an antigen binding molecule specific for the CD117 antigen, thereby generating said cell composition comprising or consisting of ventral midbrain dopaminergic progenitor cells. Cell compositions obtainable by said method are also disclosed.

Abstract: RNA encoding an immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially a neutral surface charge at physiological pH and are effective for immunisation.

Abstract: Transfer of genetic and other materials to cells is conducted in a hands-free, automated, high throughput, continuous process. A system using a microfluidic hydrodynamic sheath flow configuration includes arrangements for pushing cells from side streams containing a cell culture medium to a central stream containing an electroporation buffer. Electroporation can be conducted in an assembly in which two or more microfluidic channels are provided in a parallel configuration and in which various layers can be stacked together to form a laminate type structure.

Abstract: Compositions providing, and methods for providing and using, targeted rAAV are disclosed.

Abstract: RNA encoding an immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially a neutral surface charge at physiological pH and are effective for immunisation.

Abstract: Genetically modified CCNT1 and XPO1 genes encoding proteins that inhibit virus infection in cells. The genetically modified CCNT1 gene encodes a protein with a C261Y substitution with respect to the human CCNT1 protein. The genetically modified XPO1 gene encodes a protein with P411T, M412V, and/or F414S substitutions with respect to the human XPO1 protein. The genetically modified CCNT1 and XPO1 genes can be introduced in cells. The cells comprising the genetically modified CCNT1 and XPO1 genes can be introduced in a subject with a virus infection to treat the infection.

Abstract: RNA encoding an immunogen is delivered in a liposome for the purposes of immunisation. The liposome includes lipids which have a pKa in the range of 5.0 to 7.6 and, preferably, a tertiary amine. These liposomes can have essentially neutral surface charge at physiological pH and are effective for immunisation.

Abstract: A modified immunocyte: (1) which expresses an exogenous unmodified T cell receptor ?-chain and an exogenous T cell receptor ?-chain on the cell surface thereof; or (2) which contains a polynucleotide encoding a T cell receptor ?-chain and a polynucleotide encoding a T cell receptor ?-chain. Thus, a new tool whereby immunity can be appropriately induced in vivo is provided.