Abstract: Disclosed herein include methods, compositions, culture media, and devices for in vitro culture of synthetic embryos from mammalian pluripotent stem cells. The in vitro embryo model is generated with embryonic and extraembryonic lineages derived from embryonic stem cells through transcription-factor-mediated reprogramming and can undergo advanced development to late headfold stages.

Abstract: Provided is a method of differentiating a pluripotent stem cell of mammalian origin into a desired cell type by predicting the direction of cell differentiation to be caused by induction of expression of a transcription factor. A human gene expression correlation matrix using human cells has been newly created, and further, it has been confirmed that human pluripotent stem cells can be differentiated into a desired cell type by introducing, into the human pluripotent stem cells, a transcription factor cocktail selected from the matrix.

Abstract: The present invention relates to a method for differentiating a spherical neural mass (SNM) into retinal outer layer cells, and a composition containing the retinal outer layer cells prepared by the differentiation method. If the differentiation method of the present invention is used, the SNM can be efficiently differentiated into retinal outer layer cells, and thus the present invention can be effectively used in research development and commercialization related thereto.

Abstract: The present disclosure provides a method for separating a neural crest derived cell from peripheral blood. In the present disclosure, a mononuclear cell is separated from the peripheral blood and then directly cultured, thereby maximizing use of a neural crest stem cell with a differentiation potential to avoid loss of the neural crest stem cell. In the method of the present disclosure, a sample to be separated is derived from the peripheral blood. The method shows less trauma and low cost. Most importantly, compared to extracting the neural crest derived cell from tissues, the neural crest derived cell extracted from the peripheral blood can be used clinically as a type of biomarker.

Abstract: Provided herein are isolated neural stem cells and methods of making neural stem cells from human trophoblast stem cells. The isolated neural stem cells can be immune-privileged and express one or more protein(s). Also provided are methods for treatment of neurodegenerative diseases using suitable preparations comprising the isolated neural stem cells.

Abstract: The present disclosure relates to compositions and methods for preventing and treating acute graft-versus-host disease.

Abstract: This invention relates to the production of haemogenic endothelial cells (HECs). A population of induced pluripotent stem cells (iPSCs) is differentiated into mesoderm cells by culturing the IPSCs sequentially in first, second and third mesoderm induction media to induce differentiation into mesoderm cells. The mesoderm cells are then differentiated into HECs by culturing the mesoderm cells sequentially in first and second haemogenic endothelium (HE) induction media to induce differentiation into HECs. The HECs may be further differentiated into hematopoietic progenitor cells (HPCs) and progenitor T cells.

Abstract: Provided is a method of preparing a somatic cell including converting a differentiated somatic cell of a mammal to other somatic cell by culturing the differentiated somatic cell in a medium for inducing differentiation of the somatic cell other than the differentiated somatic cell in the presence of a TGF-? pathway inhibitor.

Abstract: Compositions and methods are described herein for transdifferentiation of multipotent stromal cells into cells that can express insulin.

Abstract: The present disclosure provides a method for preparing a composition including mesenchymal stem cells, extracellular vesicles produced by the mesenchymal stem cells, and growth factors, the composition prepared by the method, and use of the composition for treating arthritis. The composition of the present disclosure achieves the effect of treating arthritis through various efficacy experiments.

Abstract: This application relates to stem cell biology and regenerative medicine. Disclosed herein methods for isolation of skeletal stem cells, related methods, related compositions, related products, and related uses.

Abstract: An object of the present invention is to provide an approach of removing non-endocrine unintended cells coexisting with insulin-secreting cells obtained by the differentiation. The present invention relates to a method for producing an insulin-producing cell population, comprising the step of treating an insulin-producing cell population obtained by the differentiation from pluripotent stem cells with a PLK inhibitor.

Abstract: Disclosed herein are methods, compositions, kits, and agents useful for inducing ? cell maturation, and isolated populations of SC-? cells for use in various applications, such as cell therapy.

Abstract: Provided are a stable lentivirus packaging cell line and a preparation method therefor. The stable lentivirus packaging cell line contains a packaging plasmid group consisting of a pPuro.coTetR plasmid, a pVSVG plasmid, and a pGagPol-RRE-NES-cINT plasmid, wherein the pPuro.coTetR plasmid contains a CoTetR gene, the pVSVG plasnid contains a VSVG gene, and the pGagPol-RRE-NES-cINT plasmid contains GagPol and Rev genes. The stable lentivirus packaging cell line is relatively stable in terms of passage, virus production, and a genetic gene copy number, and the lentivirus produced by using the stable lentivirus packaging cell line has a high titer and a low impurity content.

Abstract: The present invention provides modified alphaviruses and compositions, methods, and kits for preparing and using, in particular AAV viral particles pseudotyped with capsids, in particular for use in gene therapy and/or diagnostics.

Abstract: Disclosed herein are cells and cell lines that are selected for retention of at least two exogenous nucleic acid constructs using a single selective pressure. Also disclosed herein are compositions and methods for generating recombinant cells and cell lines using a single selective pressure.

Abstract: The present invention is directed to isolated bacteriophages having specificity and lytic activity against strains of pathogenic E. coli, methods of using the bacteriophages, progeny and derivatives derived therefrom, to control the growth of pathogenic E. coli in various settings (e.g., food safety, environmental—including food establishments and medical settings—sanitation, urinary tract infections, modulating microbiome, prebiotics, probiotics).

Abstract: The present application discloses a recombinant Newcastle disease virus genome, a recombinant Newcastle disease virus rNDV-VEGF-Trap containing the genome and a preparation method therefor, a DNA molecule encoding the recombinant Newcastle disease virus genome, and a use of the genome and the recombinant Newcastle disease virus in the preparation of a drug for treating cancer. The recombinant Newcastle disease virus provided by the present application relates to inserting a coding gene of VEGF-Trap into the genome of the recombinant Newcastle disease virus, such that the recombinant Newcastle disease virus obtained therefrom is replicated with a strong replication capability, thereby killing host cancer cells; moreover, the recombinant Newcastle disease virus has reliable safety for non-cancer cells, and shows improved anti-tumor effect and oncolytic efficiency.

Abstract: Provided are transaminase mutants and uses thereof. The transaminase mutant is obtained by one or more amino acid mutations occurring in SEQ ID NO: 2 or is a mutant with a conserved amino acid mutation obtained by taking the sequence SEQ ID NO: 1 of a wild-type CvTA transaminase as a reference. Compared with wild-type transaminases, the catalytic activity of the mutant is improved to different degrees, so that the production efficiency of chiral amine compound synthesis may be improved.

Abstract: The invention includes a mutant Taq polymerase, which can significantly extend and amplify a target sequence where the extension conditions are time limited to as little as one second. The mutant Taq polymerase, or a biologically active fragment thereof, has one or more substitutions differing from the wild type as shown in Table I.

Abstract: The invention relates to variants of a DNA polymerase of the polX family capable of synthesizing a nucleic acid molecule without a template strand, or of a functional fragment of such a polymerase, comprising at least one mutation of a residue in at least one specific position, and to uses of said variants, in particular for the synthesis of nucleic acid molecules comprising 3?-OH modified nucleotides.

Abstract: The present disclosure provides methods and systems for amplifying and analyzing nucleic acid samples. The present disclosure provides methods for preparing cDNA and/or DNA molecules and cDNA and/or DNA libraries using modified reverse transcriptases.

Abstract: Provided herein, inter alia, are compositions and methods for treating and/or preventing conditions associated with gut inflammation caused by dysbiosis via use of exogenously administered acid phosphatases or enzymes of the GDA1_CD39 superfamily (such as apyrases).

Abstract: The invention involves the provision of recombinant algal mutants that have a genetic modification to a nucleic acid sequence encoding a trehalose biosynthetic enzyme, and/or a genetic modification to a nucleic acid encoding an RNA binding domain And in some embodiments either of these algal mutants can further have a genetic mutation to a nucleic acid sequence encoding an SGI1 polypeptide. Attenuation of one, two, or all three of these genes results in a mutant organism with increased lipid productivity. It was also discovered that one, two, three, or more genetic mutations can be accumulated or “stacked” in a particular mutant cell or organism to result in further increases in the production of lipid products. The lipid products of these mutants are useful as biofuels or for other specialty chemical products.

Abstract: A method for producing a protein encoded by a target gene, comprising the step of expressing the target gene in a bacterium of the genus Burkholderia, wherein the bacterium lacks one or more genes selected from the group consisting of BSFP_068740, BSFP_068730, and BSFP_068720, or has inhibited expression of the genes or proteins encoded by the genes.

Abstract: In one aspect, embodiments disclosed herein are directed to engineered CRISPRCas effector proteins that comprise at least one modification compared to an unmodified CRISPR-Cas effector protein that enhances binding of the of the CRISPR complex to the binding site and/or alters editing preference as compared to wild type. In certain example embodiments, the CRISPR-Cas effector protein is a Type II effector protein. In certain other example embodiments, the Type V effector protein is Cas9 or an orthologs or engineered variant thereof. Example Cas9 proteins suitable for use in the embodiments disclosed herein are discussed in further detail below.

Abstract: Compositions and methods are provided for modulating growth of a genetically modified bacterial cell present in a human organ, for modulating growth of a genetically modified bacterial cell in an organ (e.g., gut), for displacing at least a portion of a population of bacterial cells in an organ, and for facilitating gut colonization by a genetically modified bacterial cell. Also provided are genetically modified bacterial cells, e.g., cells that include a heterologous carbohydrate-utilization gene or gene set that provides for the ability to utilize as a carbon source a rare carbohydrate of interest that is utilized as a carbon source by less than 50% of bacterial cells present in a human microbiome.

Abstract: Novel polypeptides having lysozyme activity, polynucleotides encoding polypeptides having lysozyme activity, and nucleic acid constructs, vectors, and host cells comprising polynucleotides that encode polypeptides having lysozyme activity, as well as methods of producing and using such polypeptides, polynucleotides, constructs, vectors, and host cells, including, but not limited to, animal feed and animal feed additives comprising polypeptides having lysozyme activity.

Abstract: Some aspects of this disclosure provide methods for phage-assisted continuous evolution (PACE) of proteases. Some aspects of this invention provide methods for evaluating and selecting protease inhibitors based on the likelihood of the emergence of resistant proteases as determined by the protease PACE methods provided herein. Some aspects of this disclosure provide strategies, methods, and reagents for protease PACE, including fusion proteins for translating a desired protease activity into a selective advantage for phage particles encoding a protease exhibiting such an activity and improved mutagenesis-promoting expression constructs. Evolved proteases that recognize target cleavage sites which differ from their canonical cleavage site are also provided herein.

Abstract: Provided and described herein are methods and compositions for decreasing blood glucose, reducing an increase in blood glucose, and/or lowering the glycemic index of a foodstuff.

Abstract: The disclosure provides improved ADAMTS13 variants with amino acid substitutions in the linker 3 region. The disclosure also provides methods for producing and using the variants.

Abstract: The disclosure provides methods and compositions for treating blood diseases/disorders, such as sickle cell disease, hemochromatosis, hemophilia, and beta-thalassemia. For example the disclosure provides therapeutic guide RNAs that target the promotor of HBG1/2 to generate point mutations that increase expression of fetal hemoglobin. As another example, the disclosure provides therapeutic guide RNAs that target mutations in HBB, Factor VIII, and HFE to treat sickle cell disease, beta-thalassemia, hemophilia and hemochromatosis. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins are in complex with nucleic acids, such as guide RNAs (gRNAs), which target the fusion proteins to a DNA sequence (e.g., an HBG1 or HBG2 protmoter sequence, or an HFE, GBB, or F8 gene sequence).

Abstract: The disclosure provides methods and related kits, reagents, and systems for selectively deaminating unmethylated cytosine residues in nucleic acid molecules. In some embodiments, the methods and related kits, reagents, and systems are applied for methods of detecting and/or mapping methylated cytosine residues in nucleic acids. The nucleic can be RNA or DNA. Some embodiments include contacting the polynucleic acid with a bacterial cytosine deaminase, for example DddA or SsdA, or functional fragments or derivatives thereof. Representative DddA and SsdA have sequences set forth in SEQ ID NOS:1 and 2, respectively. The bacterial cytosine deaminases of the disclosure are sensitive to methylation and, thus, deaminate only unmethylated cytosines to provide a cytosine to uracil conversion. The conversion can be detected as a C•G-to-T•A transitions in subsequent sequencing analysis.

Abstract: Disclosed is an expression vector comprising a polynucleotide encoding for a glutamine synthetase with reduced activity compared to a wild type glutamine synthetase. Also disclosed are host cells, methods for preparing stable cell line, methods of producing polypeptide of interest, and kits thereof.

Abstract: The invention pertains to an ex vivo method for increasing expression of at least one of gamma globin 1 (HBG1) and 2 (HBG2). The method can be used for the treatment or prevention of a haemoglobinopathy. The method comprises a step of introducing a first and a second site-specific endonuclease into a cell, wherein the first and second site-specific endonuclease generate a first and a second double stranded break in a chromosome, thereby generating a first, an intervening second and a third chromosomal fragment, wherein i) the first fragment comprises an beta globin locus control region (LCR) a functional fragment thereof; and ii) the third fragment comprises a sequence encoding at least one of HBG1 and HBG2. The length of the second intervening fragment is at least about 5 kb, and wherein joining the first fragment to the third fragment results in operably linking the beta globin LCR to the sequence encoding at least one of HBG1 and HBG2, thereby increasing at least one of HBG1 and HBG2 protein expression.

Abstract: The disclosure provides novel methods and compositions for gene editing. In particular, the disclosure relates to compositions and methods of making modified nucleic acid donor templates for highly efficient and precise gene editing.

Abstract: Provided herein are systems and methods for drug screening single cells from a sample. A method for drug screening may comprise treating various single cell samples with different drugs or drug combinations, labeling of treated cells with a labeling agent comprising a sample barcode, and processing the treated, labeled cells to generate nucleic acid libraries for sequencing. One or more processes of the methods described herein may be performed within a partition, such as a droplet or well.

Abstract: The invention relates to a method of identifying a genomic target for a test stimulus that is capable of modulating a cell phenotype, comprising: a) providing a population of cells that are phenotypically negative in response to the test stimulus; b) modifying the population of cells by random insertion into the cell genome of a gain-in-function construct; c) contacting the modified cell population with the test stimulus; d) screening the exposed modified cell population to identify modified cells that are phenotypically positive in response to the test stimulus; and e) identify a gene or genes associated with said positive phenotype thereby identifying the genomic target of the test stimulus.

Abstract: Provided herein are compositions comprising a CRISPR array comprising one or more crRNA sequences and a 5? direct repeat (DR) sequence linked to a barcode guide RNA (bcgRNA), wherein the bcgRNA comprises from 5? to 3? (a) a barcode sequence, and (b) a reverse-transcription handle. Also provided are methods that comprise using the described CRISPR arrays to introduce one or perturbations in a single cell transcriptome.

Abstract: The invention relates to saRNAs targeting a C/EBP? transcript and therapeutic compositions comprising said saRNAs. Methods of using the therapeutic compositions are also provided.

Abstract: The subject matter disclosed herein is directed to modulating gene expression using siRNA compositions and methods directed to affecting key cell populations supporting the growth and metastasis of cancer to affect the beneficial treatment, remission or removal of the underlying tumor in a patient.

Abstract: The present disclosure relates to methods of treating osteoarthritis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a USP16 inhibitor.

Abstract: Provided herein are genetic circuits and encoded RNA transcripts that produce an output molecule in response to an RNA cleavage event that removes a degradation signal. In some embodiments, the genetic circuits described herein may be used for detecting RNA cleaver activities (e.g., in a cell). Methods of using the genetic circuits described herein in diagnostic or therapeutic applications are also provided.

Abstract: Disclosed herein are compositions for and methods of generating chimeric RNA molecules and methods of treating and/or preventing a genetic disease or disorder using chimeric RNA molecules.

Abstract: The present application relates to an RNA interference (RNAi) agent for inhibiting the expression of hepatitis B virus and uses thereof, and to an RNAi agent that inhibits the expression of hepatitis B virus and a pharmaceutical composition including the RNAi agent for amelioration or treatment of diseases caused by hepatitis B virus infection.

Abstract: The invention provides a diagnostic kit for metastasis and invasion of breast cancer and a use of an shRNA molecule for silencing expression of human LINC01614. The shRNAs obtained by the invention can interfere with the expression of LINC01614, thereby reducing the migration and invasion ability of tumor cells, inhibiting the expression of EMT proteins, and inhibiting tumor formation and lung metastasis in an animal model in vivo. The invention provides a new solution for targeted therapy of breast cancer. Therefore, the kit for diagnosing metastasis and invasion of breast cancer and the medication for treating metastasis and invasion of breast cancer are developed. The invention provides a new way and strategy for diagnosing and treating metastasis and invasion of breast cancer.

Abstract: A method of increasing an amount of Chromodomain Helicase DNA Binding Protein 2 (CHD2) in a neuronal cell is provided. The method comprising introducing into the cell a nucleic acid agent that down-regulates activity or expression of human Chaserr, wherein the nucleic acid agent is directed at the last exon of human Chaserr, thereby increasing the amount of CHD2 in the neuronal cell.

Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a prion protein (PRNP) gene, as well as methods of inhibiting expression of a PRNP gene and methods of treating subjects having a PRNP-associated disease or disorder, e.g., Prion diseases, using such dsRNAi agents and compositions.

Abstract: The present disclosure, in part, relates to novel, aptamers targeting ?-synuclein. The present disclosure includes methods for making and methods of using aptamers targeting ?-synuclein.

Abstract: The invention provides novel uses of sequence-specific or sequence-directed endonucleases for molecular plant breeding. The invention also provides novel plant transformation vectors and expression cassettes, which include novel combinations of an endonuclease with plant expression and transformation elements. Plants and derivatives thereof produced by such methods are also provided.