Abstract: The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

Abstract: Compositions comprising synthetic membrane-receiver complexes, methods of generating synthetic membrane-receiver complexes, and methods of treating or preventing diseases, disorders or conditions therewith.

Abstract: The invention relates to an isolated cell having, after culturing a pluripotent stem cell (PSC) in a medium comprising a WNT agonist and an ACTIVIN antagonist, increased HOXA gene expression relative to a PSC not cultured in a medium comprising a WNT agonist and an ACTIVIN antagonist, wherein the cell with increased HOXA gene expression is capable of generating a definitive haematopoietic stem/precursor cell. The invention also relates to use of the cell for generating a definitive haematopoietic stem/precursor cell, and a method for differentiating a PSC into a definitive haematopoietic stem/precursor cell and a definitive haematopoietic stem/progenitor cell differentiated from a PSC by the method. The invention further relates to a therapeutic composition comprising a cell of the invention, and to therapeutic methods and uses of a cell of the invention.

Abstract: This disclosure relates to methods of generating pacemaker cells for use in therapeutic strategies that address a heart that beats abnormally. In certain embodiments, one mixes cells with an epithelial-to-mesenchymal transformation inhibitor in combination with a nucleic acid encoding a transcription factor such as a vector that encodes a transcription factor such as Tbx18 in operable combination with a eukaryotic promoter to produce pacemaker cells that are then transplanted into the heart.

Abstract: Provided are a method for producing stem cell-derived extracellular vesicles by using a three-dimensional cell culture process, use of three-dimensional cell aggregates of stem cells in producing extracellular vesicles, a culture of three-dimensional cell aggregates of stem cells comprising a high concentration of extracellular vesicles, and a pharmaceutical composition comprising the culture.

Abstract: The present invention relates to immortalised chicken embryonic epithelial kidney cells, to cell cultures comprising such immortalised cells, to vaccines comprising such cells, to methods for the replication of avian viruses on such cells, and to methods for the preparation of such cells and such vaccines.

Abstract: Disclosed is a method for producing an in vitro model for blood-brain barrier, including (a) a culturing conditionally immortalized astrocytes on one surface of a porous membrane and culturing conditionally immortalized brain pericytes on the other surface of the porous membrane, until both of the cells become a sheet; (b) culturing conditionally immortalized brain microvascular endothelial cells in a culture vessel, until the cells become a sheet; (c) peeling off the sheet of conditionally immortalized brain microvascular endothelial cells; (d) allowing the sheet of conditionally immortalized brain microvascular endothelial cells to come into contact with the sheet of conditionally immortalized brain pericytes, so that the sheets are arranged in layers; and (e) co-culturing a cell culture comprising three layers consisting of the sheet of conditionally immortalized brain microvascular endothelial cells, the sheet of conditionally immortalized brain pericytes, and the sheet of conditionally immortalized astro

Abstract: In a method for manufacturing a modified enterovirus of ECHO 7 type by modification of native ECHO 7 virus, isolated by a known method from human feces and identified by genome sequence, the modification is performed initially conducting the virus adaptation in cancer cells, attenuated by anti-cancer agent dacarbazine, further passaging the modified virus in human embryonal fibroblast culture, followed by propagation in human melanoma cells and further passaging in human embryonal fibroblast culture, that was treated by ribavirin, isolation and purification by known method. The modified virus is suitable for treating various tumours.

Abstract: The present invention provides compositions of CD180 targeting molecules coupled to heterologous antigens, and their use in treating and/or limiting disease.

Abstract: The present invention relates to DEV and the uses thereof. The invention is particularly suited to vaccinate poultry against avian pathogens.

Abstract: The present invention relates to DEV and the uses thereof. The invention is particularly suited to vaccinate poultry against avian pathogens.

Abstract: The present disclosure provides engineered ketoreductase enzymes having improved properties as compared to a naturally occurring wild-type ketoreductase enzyme. Also provided are polynucleotides encoding the engineered ketoreductase enzymes, host cells capable of expressing the engineered ketoreductase enzymes, and methods of using the engineered ketoreductase enzymes to synthesize a variety of chiral compounds.

Abstract: The subject disclosure features, in one aspect, a method for producing lipids enriched for EPA, comprising modifying a microalga to increase expression of PFA1, and/or PFA3, and culturing the modified microalga under conditions which allow the expression of PFA1, and/or PFA3, wherein lipids enriched for EPA are produced. Also featured is a recombinant microalga in which PFA1, and/or PFA3, is overexpressed. Such recombinant microalgae have been demonstrated herein to produce very favorable fatty acid lipid profiles (e.g., increased levels of EPA, increased ratio of EPA:DHA, decreased levels of DPA n-6, etc.).

Abstract: Presented herein are polymerase enzymes for improved incorporation of nucleotide analogues, in particular nucleotides which are modified at the 3? sugar hydroxyl, as well as methods and kits using the same.

Abstract: The present invention relates to polymerase HBV mutant polypeptides comprising a mutated polymerase domain which is functionally disrupted for polymerase activity and fusion proteins comprising such polymerase mutant polypeptide. The present invention also relates to a nucleic acid molecule and an expression vector for expressing said polymerase mutant polypeptide as well as a composition which can be used for eliciting an immune response to HBV with the goal of providing a protective or therapeutic effect against HBV infection.

Abstract: Disclosed herein are recombinant polynucleotide sequences, vectors, host cells and methods for producing astaxanthin. The recombinant polynucleotide sequence is designed to provide a higher level of astaxanthin precursors via a shorter metabolic pathway, and thereby attains higher level of end products (e.g., astaxanthin) with desired stereoisomeric form and/or esterified form.

Abstract: Disclosed are compositions and methods relating to variant alpha-amylases. The variant alpha-amylases are useful, for example, for starch liquefaction and saccharification, for cleaning starchy stains in laundry, dishwashing, and other applications, for textile processing (e.g., desizing), in animal feed for improving digestibility, and for baking and brewing.

Abstract: Multi-stage acoustophoretic devices for continuously separating a second fluid or a particulate from a host fluid are disclosed. Methods of operating the multi-stage acoustophoretic devices are also disclosed. The systems may include multiple acoustophoretic devices fluidly connected to one another in series, each acoustophoretic device comprising a flow chamber, an ultrasonic transducer capable of creating a multi-dimensional acoustic standing wave, and a reflector. The systems can further include pumps and flowmeters.

Abstract: The invention relates to a device (1) for applying an electric field to a suspension of cells, cell derivatives, organelles, sub-cellular particles and/or vesicles, comprising at least one chamber (6) which comprises at least two electrodes (4), and at least one separating element (13) which is movable within the chamber (6) between two terminal points (14, 15) and, if it is in a position between the terminal points (14, 15), separates at least one first compartment (26) of the chamber (6) from at least one second compartment (27) of the chamber (6).

Abstract: The present disclosure relates to compositions and methods for modifying a gene sequence, and for systems for delivering such compositions. For example, the disclosure relates to modifying a gene sequence using a CRISPR-Cas9 or other nucleic acid editing system, and methods and delivery systems for achieving such gene modification, such as viral or non-viral delivery systems.

Abstract: By this invention, for the first time, a method for high-efficiency site-specific genetic engineering, utilizing either native or heterologous CRISPR-Cas9 systems, in the anaerobic bacterium Clostridium pasteurianum, is provided. Application of CRISPR-Cas9 systems has revolutionized genome editing across all domains of life. Here we report implementation of the heterologous Type CRISPR-Cas9 system in Clostridium pasteurianum for markerless genome editing. Since 74% of species harbor CRISPR-Cas loci in Clostridium, we also explored the prospect of co-opting host-encoded CRISPR-Cas machinery for genome editing. Motivation for this work was bolstered from the observation that plasmids expressing heterologous cas9 result in poor transformation of Clostridium. To address this barrier and establish proof-of-concept, we focus on characterization and exploitation of the C. pasteurianum Type CRISPR-Cas system.

Abstract: Described herein are methods and means for reliably releasing maternal and/or paternal DNA from single seeds without substantially affecting the subsequent germination of the seeds. The methods are particularly suited for genome analysis of small grain cereals, including wheat. The methods may include enzymatic treatments for improved DNA recovery.

Abstract: There is described herein, a method of capturing cell-free methylated DNA from a sample having less than 100 mg of cell-free DNA, comprising the steps of: subjecting the sample to library preparation to permit subsequent sequencing of the cell-free methylated DNA; adding a first amount of filler DNA to the sample, wherein at least a portion of the filler DNA is methylated; denaturing the sample; and capturing cell-free methylated DNA using a binder selective for methylated polynucleotides.

Abstract: A rack for holding samples and various reagents, wherein the rack may be used for loading the samples and reagents prior to using the reagents. The rack accepts complementary reagent holders, each of which contain a set of reagents for carrying out a predetermined processing operation, such as preparing biological samples for amplifying and detecting polynucleotides extracted from the samples.

Abstract: The present disclosure provides methods and kits for isolating miRNAs from biological fluids.

Abstract: The present disclosure relates to novel peptides and their uses including, proline-rich peptides that are useful for displaying a protein of interest at the surfaces of a host cell such as a yeast. Polynucleotides, proteins, vectors and host cells that comprise or encode the novel proline-rich peptides, including libraries comprising such polynucleotides, proteins, vectors and/or host cells that comprise or encode novel proline-rich peptides are provided. Methods and materials for display and expression of proteins of interest are provided. Methods and materials are also provided by the present disclosure for isolating peptides capable of displaying a protein of interest (e.g., a marker protein), for generating libraries to display and/or express proteins of interest (e.g., antibodies such as humanized antibodies), for generating secretion vectors for such proteins of interest, and for generating proteins of interest (e.g., antibodies).

Abstract: The present disclosure provides a combinatorial metabolic engineering system based on an orthogonal tri-functional CRISPR system that combines transcriptional activation, transcriptional interference, and gene deletion (CRISPR-AID). This strategy enables perturbation of the metabolic and regulatory networks in a modular, parallel, and high throughput manner. The present disclosure further provides a multi-functional genome-wide CRISPR (MAGIC) system for high throughput genotype-phenotype mapping.

Abstract: The present invention relates to a method for producing a panel of cells (i.e. a cell library) expressing various different mutant variants of a protein of interest, wherein only one of said mutant variants is expressed per cell from a single gene copy. The present invention also relates to a method or cell library for identifying a mutant variant of a protein of interest having a different or modified biological activity as compared to the corresponding wild-type protein of interest. According to the present invention the identified mutant variant of a protein of interest may be applied for white biotechnology.

Abstract: Methods, systems and related compositions are provided to perform single-cell marking of a nucleic acid and/or protein in a sample based on in-cell or in-organelle barcoding of nucleic acid and/or protein complexes of the cell or organelle; the methods and systems herein described are configured to provide in-cell or in-organelle single-cell marked nucleic acid and/or protein complexes comprising a single-cell, cell-specific, or a single-cell organelle-specific marker.

Abstract: System and method for enhancing ligation of nucleic acid portions using focused acoustic energy.

Abstract: Compositions and methods to prevent, inhibit or treat aveolar or periodontal bone loss, enhance bone regeneration, prevent, inhibit or treat peri-implantitis or periodontitis, e.g., periodontitis or peri-implantitis associated with bone loss, or to prevent, inhibit or treat osteoarthritis are provided.

Abstract: Disclosed herein are compositions and methods for enhancing T-cell activity by modulating a miRNA so as to improve T-cell therapies, infectious disease therapies and down-regulate auto-immune responses.

Abstract: The invention is directed to compositions and methods for treating or reducing the likelihood of the development of epilepsy in an individual. The method comprises administering to the central nervous system of an individual in need of such treatment a therapeutically effective amount of an agent capable of increasing the expression and/or activity of miR-128.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing transth:yretin (TTR) target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Abstract: The present invention provides for a double stranded RNA comprising a first RNA sequence and a second RNA sequence wherein the first and second RNA sequence are substantially complementary, wherein the first RNA sequence has a sequence length of at least 19 nucleotides and is substantially complementary to SEQ ID NO. 1. Said double stranded RNA is for use in inducing RNAi against Huntingtin exon 1 sequences. The double stranded RNA of to the invention was capable of reducing neuronal cell death and huntingtin aggregates in an animal model.

Abstract: An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 214.

Abstract: Provided herein are methods and compositions for treatment and/or prevention of liver disease. Aspects of the present disclosure relate to the engineering of a quiescent Hepatic Stellate Cell, and use of the engineered quiescent Hepatic Stellate Cell, or population thereof in the treatment and/or prevention of liver disease.

Abstract: Methods of using B2 or Alu nucleic acids, or antisense oligonucleotides that modulate the EZH2/B2 or EZH2/Alu interaction and have the capacity to alter cleavage of B2 and Alu RNA, for increasing or decreasing cell and organismal viability.

Abstract: Described herein are compositions and methods for the inhibition of miR-122 activity. The compositions have certain nucleoside modifications that yield potent inhibitors of miR-122 activity. The compounds may comprise conjugates to facilitate delivery to the liver. The compositions may be administered to subjects infected with hepatitis C virus, as a treatment for hepatitis C virus and related conditions.

Abstract: The invention refers to an oligonucleotide consisting of 10 to 20 nucleotides of selected regions of the TGF-beta1, TGF-beta2 or TGF-beta3 nucleic acid sequence, which comprises modified nucleotides such as LNA, ENA, polyalkylene oxide-, 2?-fluoro, 2?-O-methoxy and/or 2?-O-methyl modified nucleotides. The invention further relates to pharmaceutical compositions comprising such oligonucleotide, wherein the composition or the oligonucleotide is used in a method for the prevention and/or treatment of glaucoma, posterior capsular opacification, dry eye, Marfan or Loeys-Dietz syndrome, riboblastoma, choroidcarcinoma, macular degeneration, such as age-related macular degeneration, diabetic macular endma, or cataract.

Abstract: RNA interference is provided for inhibition of HIF1A mRNA expression for treating patients with ocular angiogenesis, particularly for treating retinal edema, diabetic retinopathy, sequela associated with retinal ischemia, posterior segment neovascularization (PSNV), and neovascular glaucoma, and for treating patients at risk of developing such conditions.

Abstract: A method for inhibiting metastasis of cancer cells is provided. Inhibitors of heparan sulfate (HS) or hyaluronic acid (HA) are applied to a tumor or a surgical location after removal of the bulk of the tumor. The inhibitors enzymatically cleave surface HS or HA; genetically modify cancer cells to decrease HS or HA production or interfere with the signaling pathway between HS or HA and a MMP or syndecan.

Abstract: The present invention relates to RNA-based methods for inhibiting the expression of the superoxide dismutase 1 (SOD-1) gene. Recombinant adeno-associated viruses of the invention deliver DNAs encoding RNAs that knock down the expression of SOD-1. The methods have application in the treatment of amyotrophic lateral sclerosis.

Abstract: The invention relates to an oligonucleotide that supresses the expression of an allele carrying a dominant mutation that causes hereditary sensory neuropathy type I (HSN1), wherein the suppression takes place through hybridisation of said oligonucleotide to the DNA of said allele or to an RNA transcript of said allele, and which either does not suppress the expression of a wild-type allele not containing the dominant mutation or suppresses the expression of said wild-type allele to a lesser extent than it suppresses the expression of the dominant mutant allele; and also pharmaceutical compositions comprising oligonucleotides of the invention and treatments of HSN1 using such oligonucleotides.

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.

Abstract: Provided is a linked polynucleotide in which polynucleotides encoding a promoter, an anchoring motif, and a dehalogenase, respectively, are operatively linked to one another; a host cell including the linked polynucleotide; and a method of reducing a concentration of a fluorine-containing compound in a sample by using the host cell.

Abstract: Methods of generating fusion protein variants are provided that comprise introducing sequence diversity at the junction region or regions in the fusion and allows for the generation of variants having a desired activity. Examples include immunoglobulins comprising a domain or polypeptide inserted into, or replacing, a CDR. Also provided are polynucleotides encoding a fusion protein and comprising two or more RSSs, and compositions and host cells comprising same, as well as fusion proteins variants produced by the described methods.

Abstract: A translational control method using an RNA-protein interaction motif is provided. The method comprises a step of introducing an mRNA having: a 5?UTR regulation structure comprising: (1) a cap structure at the 5? terminus, (2) a spacer positioned on the 3? side of the cap structure, and (3) one or more RNA motifs positioned on the 3? side of the spacer, which comprises an RNA-protein interaction motif-derived nucleotide sequence or a variant thereof; and a nucleotide sequence encoding a target protein gene on the 3? side of the 5?UTR regulation structure, into a cell in the presence of a protein specifically binding to the RNA motifs, wherein a translational level is decreased as the number of bases of the spacer decreases, and the translational level is decreased as the number of the RNA motifs increases.

Abstract: Signal sequences useful for targeting proteins and peptides to the surface of endospores produced by Paenibacillus family members and methods of using the same are provided. The display of heterologous molecules, such as peptides, polypeptides and other recombinant constructs, on the spore surface of Paenibacillus family members, using particular N-terminal targeting sequences and derivatives of the same, are also provided.

Abstract: The invention discloses a method for improving the yield of Bacillus subtilis acetylglucosamine, which belongs to the technical field of genetic engineering. In the invention, the recombinant Bacillus subtilis S5 (S5-PxylA-glmS-P43-GNA1) is taken as a starting strain, and the glmS ribozyme is integrated into the mid of rbs and the promoter sequence of the glmM and pfkA gene, respectively. The ribozyme mutant has the advantage of prolonging the stability of the mRNA and integrated into the mid of rbs and the promoter sequence of the pgi gene. The yield of GlcNAc of the recombinant strain reaches 11.79-20.05 g/L. This laid the foundation for the further metabolic engineering of Bacillus subtilis to produce GlcNAc.