Abstract: Provided herein are methods to increase the culture density and/or thickness of a cellular biomass in a cultivation infrastructure, to improve the culture of cells in the absence of serum in a cultivation infrastructure, and to promote anchorage-independent growth of a cellular biomass in a cultivation infrastructure. The methods comprise inhibiting the HIPPO signaling pathway, for example, by activating YAP1, activating TAZ, and/or inhibiting MOB1, LATS1 kinase, LATS2 kinase, WW45, MST1 kinase, and/or MST2 kinase in the cellular biomass. In some embodiments, the cellular biomass is harvested from the cultivation infrastructure for the formulation of cell-based food products or ingredients, such as animal meat manufactured from cells in an ex vivo process or for therapeutic applications such as organ or tissue transplantation or grafting.

Abstract: A method of obtaining a pluripotent-like multipotent cell, including providing a cell of a first type which is not a pluripotent-like multipotent cell; contacting the cell of a first type with an agent capable of remodeling the chromatin and/or DNA of the cell; transiently increasing expression of at least one pluripotent gene regulator in the cell of a first type, to a level at which the at least one pluripotent gene regulator is capable of driving transformation of the cell of a first type into the pluripotent-like multipotent cell; and placing or maintaining the cell in a differentiation medium and maintaining intracellular levels of the at least one pluripotent gene regulator for a sufficient period of time to allow a stable pluripotent-like multipotent cell to be obtained; wherein the pluripotent-like multipotent cell so obtained does not exhibit teratoma formation in vivo.

Abstract: Provided is a method for separating and extracting mesenchymal stem cells from the human umbilical cord. The method uses healthy neonatal umbilical cord tissue; after cleaning and disinfection, mechanically pulverising same, separating the Wharton's jelly, and after treating with erythrocyte lysate, carrying out suspension culture in a serum-free culture medium. Replacing the liquid every 3-5 days; after the plate adherence rate reaches 30-70%, carrying out trypsin digestion, and then collecting the cells by centrifugation for passage amplification, until the rate of confluence of the cells reaches 80-90% confluence, thereby obtaining high purity umbilical cord mesenchymal stem cells.

Abstract: Methods to form a novel aminoglycoside based hydrogel for high-throughput generation of 3D dormant, relapsed and micrometastatic tumor microenvironments are disclosed. In addition, methods of screening agents against tumor cells grown in the 3D environments disclosed herein that include, for example, screening of lead drugs and therapies for an effect on dormant, relapsed and/or micrometastatic tumor cells.

Abstract: The present invention provides a method for maintenance and expansion of a colon cancer stem cell or induction of a colon cancer organoid. In addition, the present invention provides a medicament screening system using a colon cancer stem cell maintained and expanded or a colon cancer organoid induced by the method.

Abstract: Methods of preparing naive human pluripotent stem cells are described. The methods include the use of xeno-free media and do not include the use of feeder cells.

Abstract: Compositions and methods are disclosed for producing polymer scaffolds for tissue engineering and drug testing. The scaffolds comprise a high molecular weight polymer having an external surface functionalized with a low molecular weight polymer to which cell surface binding molecules are attached for enhancing cell adherence to the scaffold.

Abstract: Described herein are compositions and kits comprising recombinant adeno-associated viruses (rAAVs) with tropisms showing increased specificity and efficiency of viral transduction in targeted cell-types, for e.g., the brain, and lung. The rAAV compositions described herein also have tropisms showing decreased specificity and decreased efficiency of viral transduction in an off-target cell type, for e.g., the liver. The rAAV compositions described herein encapsidate a transgene, such a therapeutic nucleic acid. Upon systemic delivery to a subject, the rAAV is capable of increased specificity and increased transduction of the transgene in a target cell-type, as compared to a parental or reference AAV.

Abstract: Described are compositions comprising enveloped viruses that are not MVA, a sulfate salt at a concentration of about 5 mM to about 300 mM and a buffer, and the composition has a pH of about 6.0 to about 8.5. It also discloses methods for stabilizing an enveloped virus composition by preparing said viral formulation.

Abstract: Provided herein are genetically engineered Pichinde viruses that include three ambisense genomic segments. The first genomic segment includes a coding region encoding a Z protein and a coding region encoding a L RdRp protein. The second genomic segment includes a coding region encoding a nucleoprotein (NP) and the third genomic segment includes a coding region encoding a glycoprotein. Each of the second and third genomic segments optionally include an additional coding region that may encode an antigen or a detectable marker. Also provided herein is a reverse genetics system for making a genetically engineered Pichinde virus, and a collection of vectors that can be used to produce a genetically engineered Pichinde virus. Further provided are methods for using a reverse genetics system, and methods for producing an immune response in a subject.

Abstract: A recombinant protein, including: (a) alpha subunit of an FAD-GDH; and (b) a minimal cytochrome c peptide is provided. Additionally, an electrode coupled to a recombinant protein, the recombinant protein made of: (a) a cofactor of a redox enzyme; (b) a redox enzyme; (c) a linker moiety configured to link any one of: the cofactor or the enzyme to an electron transfer (ET) domain; and (d) an ET domain, is also provided. Methods for: (a) transferring an electron to an electrode, by coupling the recombinant protein an electrode; and (b) quantifying the amount of an analyte e.g., glucose are also provided.

Abstract: The invention refers to polypeptides with polysaccharide monooxygenase activity, to a host cell that expresses them, preferably a Myceliophthora thermophila cell that recombinantly expresses at least one of these polypeptides, to an enzymatic composition comprising at least one of these polypeptides, preferably together with other cellulolytic enzymes, the use of this host cell, of at least one of the polypeptides with polysaccharide monooxygenase activity or of the enzymatic composition for the degradation of cellulosic biomass and to a process for the production of bioproducts, preferably bioethanol, including the use of this host cell, of at least one of the polypeptides of the invention or of the enzymatic composition of the invention.

Abstract: The present invention is directed to a producing a DNA methyltransferase in a recombinant host cell, wherein the DNA methyltransferase methylates DNA resulting in a DNA containing 5-methylcytosine within the recognition sequence GCNGC and wherein the DNA methyltransferase comprises less than (35) amino acid residues between amino acid residue (72) and amino acid residue (106) according to the numbering of SEQ ID NO: 33. Furthermore, the present invention is directed to the use of such DNA methyltransferase for the production of bacterial transformants comprising the steps of (a) introducing into a first bacterial host cell a polynucleotide comprising a polynucleotide sequence encoding the DNA methyltransferase to produce a methylated DNA and (b) transferring the methylated DNA from the first bacterial host cell into a second bacterial host cell, wherein the second bacterial host cell comprises a restriction endonuclease able to degrade the DNA but unable to degrade the methylated DNA.

Abstract: In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. The mutant toxin may include a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to methods and compositions for use in culturing Clostridium difficile and in producing C. difficile toxins.

Abstract: In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.

Abstract: The present invention is directed to ligand binding molecules and uses thereof to modulate angiogenesis and/or lymphangiogenesis.

Abstract: The present invention relates to a chimeric enzyme comprising or consisting of at least one catalytic domain of a capping enzyme and at least one RNA-binding domain of a protein-RNA tethering system as well as its application for the production of an RNA molecule with a 5?-terminal cap.

Abstract: A process of recovering oil, comprising (a) converting a starch-containing material into dextrins with an alpha-amylase; (b) saccharifying the dextrins using a carbohydrate source generating enzyme to form a sugar; (c) fermenting the sugar in a fermentation medium into a fermentation product using a fermenting organism; (d) recovering the fermentation product to form a whole stillage; (e) separating the whole stillage into thin stillage and wet cake; (e?) optionally concentrating the thin stillage into syrup; (f) recovering oil from the thin stillage and/or optionally the syrup, wherein a protease and a phospholipase are present and/or added during steps (a) to (c). Use of a protease and a phospholipase for increasing oil recovery yields from thin stillage and/or syrup in a fermentation product production process.

Abstract: Methods and constructs for the multiplex expression of highly active CRISPR guide RNAs (gRNAs) from RNA Polymerase II and III promoters, optionally in mammalian cells.

Abstract: The present invention concerns an improved method for extracting ?-amylases from a soluble fraction of a starch plant, said method comprising a step of clarification by microfiltration and a step of concentration and purification by ultrafiltration. This method is characterised in that it uses a protease during the microfiltration step, making it possible to greatly reduce the fouling of the membranes used, which increases the production time before washing. Simultaneously, perfectly clear permeates are obtained, which assists with the subsequent ultrafiltration step and makes it possible to improve the transmission of ?-amylase. Finally, the protease has no negative effect on the ?-amylase activity.

Abstract: The present invention relates to a method of cellulases enzymes production by Penicillium funiculosum MRJ-16 using minimum media components and/or low cost media components like cellulose or pretreated lignocellulosic biomass as carbon source and soya flour or defatted soya flour or de-oiled soya cake as nitrogen source. The present invention also provides a method for production of high titer of cellulases and hemicellulases enzymes using Penicillium funiculosum MRJ-16 using minimum media and/or low cost media components.

Abstract: The present invention relates to polypeptides having beta-glucanase activity, catalytic domains. beta-glucan binding domains and polynucleotides encoding the polypeptides, catalytic domains or beta-glucan binding domains. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides, catalytic domains or beta-glucan binding domains. The invention further relates to cleaning or detergent compositions comprising polypeptides exhibiting beta-glucanase activity and one or more amylases and/or one or more proteases and uses thereof in cleaning or detergent applications and processes such as cleaning hard-surfaces, dish wash and laundering.

Abstract: Improved processes for producing ethanol from starch-containing materials by the combined use of at least one endoprotease and at least one exo-protease in an SSF process are disclosed. More particularly the exo-protease should make up at least 5% (w/w) of the protease mixture.

Abstract: The present disclosure relates to proteases for improving alcoholic fermentation. The proteases are expressed from a recombinant host cell. The present disclosure also provides a population of recombinant host cells expressing an heterologous protease that can be used in combination with recombinant host cells expressing an heterologous glucoamylase and/or an heterologous glycerol reduction system.

Abstract: Disclosed are methods and compositions for treating propionic academia based on mRNA therapy.

Abstract: The present invention offers a new approach for highly multiplexed, programmable antiviral therapies that directly target viral RNA, and can be flexibly adapted to target novel viruses or emerging outbreak pathogens. Class 2, type VI CRISPR system-based therapies can be used in combination with existing antiviral compounds for viruses where such compounds exist, either by increasing their efficacy or by preventing the evolution of specific drug resistance mutations. Perhaps most excitingly, if a virus evolves resistance to a specific guide RNA sequence, it is easy to switch to a different guide RNA sequence, or to design a new guide sequence to target the new mutation. Such approaches should prevent the widespread development of resistance to Class 2, type VI CRISPR system-based therapies.

Abstract: The invention relates to methods of producing eukaryotic cell libraries encoding a repertoire of binding molecules (“binders”), wherein the methods use a site-specific nuclease for targeted cleavage of cellular DNA to enhance site-specific integration of binder genes through endogenous cellular repair mechanisms. Populations of eukaryotic cells are produced in which a repertoire of genes encoding binders are integrated into a desired locus in cellular DNA (e.g., a genomic locus) allowing expression of the encoded binding molecule, thereby creating a population of cells expressing different binders.

Abstract: The invention relates to methods of producing eukaryotic cell libraries encoding a repertoire of binding molecules (“binders”), wherein the methods use a site-specific nuclease for targeted cleavage of cellular DNA to enhance site-specific integration of binder genes through endogenous cellular repair mechanisms. Populations of eukaryotic cells are produced in which a repertoire of genes encoding binders are integrated into a desired locus in cellular DNA (e.g., a genomic locus) allowing expression of the encoded binding molecule, thereby creating a population of cells expressing different binders.

Abstract: The invention relates to methods of producing eukaryotic cell libraries encoding a repertoire of binding molecules (“binders”), wherein the methods use a site-specific nuclease for targeted cleavage of cellular DNA to enhance site-specific integration of binder genes through endogenous cellular repair mechanisms. Populations of eukaryotic cells are produced in which a repertoire of genes encoding binders are integrated into a desired locus in cellular DNA (e.g., a genomic locus) allowing expression of the encoded binding molecule, thereby creating a population of cells expressing different binders.

Abstract: The present invention relates to a composition for viral RNA extraction and a viral RNA extraction method using the same, wherein various contaminants (e.g., fungi, bacteria, pollens, etc.) can be effectively removed from samples and thus the diagnosis of sample-derived viruses can be attained more sensitively, and more cheap reagents compared with existing compositions for RNA extraction are used and thus the scales of diagnosis tests of disease-mediated viruses and various monitoring programs can be further enlarged, thereby contributing to public health.

Abstract: Populations of target capture probes are provided that are useful for nucleic acid separation and purification. The probes of the population comprise a first region that is at least about 12 residues in length and comprises a poly(r) sequence comprising (i) a randomized sequence comprising G and A nucleotides, or (ii) a non-randomized repeating (A and G) sequence; and a second region comprising a first specific binding partner (SBP), wherein the SBP is capable of specifically binding a second specific binding partner (SBP2). Related combinations, methods, uses, kits, and reaction mixtures are also provided.

Abstract: Recombinant nucleic acids comprising a protein coding sequence of a multidomain protein, wherein the protein coding sequence comprises at least one synthetic attC recombination site are provided. Cells comprising the recombinant nucleic acids and methods of making the recombinant nucleic acids are also provided, among other things.

Abstract: The present invention generally relates to compositions, methods applications and screens used in functional genomics that focus on gene function in a cell and that may use vector systems and other aspects related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas systems and components thereof. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system.

Abstract: Provided are methods and compositions for identifying binding polypeptides (e.g., antibodies or antigen binding fragments thereof) that specifically binds to a cell-surface antigen. The methods of the invention generally comprise contacting a variegated nucleic acid-display library of binding polypeptides with a cell-surface antigen displayed on the exterior surface of a cell; and isolating from the library at least one library member that specifically binds to the cell-surface antigen on the exterior surface of the cell. Also provided are novel nucleic acid display libraries (e.g., DNA display libraries) useful in the methods of the invention.

Abstract: Methods and systems are provided for sample preparation techniques and sequencing of macromolecular constituents of cells and other biological materials.

Abstract: The present invention relates to a pharmaceutical composition comprising (i) a compound promoting the expression and/or the activity of one or more long non-coding RNAs (lncRNAs) selected from SEQ ID NOs 12, 8 to 11 and 13; and/or (ii)a compound inhibiting the expression and/or the activity of one or more lncRNAs selected from SEQ ID NOs 1 to 7, 27 and 28. The present invention also relates to a compound (i) promoting the expression and/or the activity of one or more lncRNAs selected from SEQ ID NOs 12, 8 to 11 and 13; and/or (ii) inhibiting the expression and/or the activity of one or more lncRNAs selected from SEQ ID NOs 1 to 7, 27 and 28 for use in treating or preventing cardiac hypertrophy.

Abstract: The invention relates to the field of cell culture technology. It concerns the knockdown, using RNA interference, or gene knockout, of activating transcription factor 6 beta (ATF6B), or the combination of ceramide synthase 2 (CERS2) and TBC1 domain family member 20 (TBC1 D20) proteins, which play central roles in the cellular secretion pathway. This downregulation leads to improved secretion of biopharmaceutically relevant products produced in mammalian cells. The invention specifically relates to mammalian cells having enhanced secretion of a recombinant therapeutic protein compared to a control cell, a method of producing said mammalian cell, a method for the production of a recombinant secreted therapeutic protein and the use of said mammalian cell for increasing the yield of a recombinant secreted therapeutic protein.

Abstract: Provided herein are methods for the treatment of polycystic kidney disease, including autosomal dominant polycystic kidney disease, using modified oligonucleotides targeted to miR-17.

Abstract: This invention generally relates to a composition and method of using mam-made small RNAs, such as small interfering RNAs (siRNA), microRNAs (miRNA) and their hairpin-like precursors (pre-miRNA), as tumor suppressing anti-cancer drugs for treating human tumors and cancers, in particular, but not limited, for treating skin (melanoma), blood (leukemia), prostate, breast, liver and lung cancers as well as various neoplastic tumors, such as brain tumors and teratocarcinomas that contain a variety of tumorous and cancerous cells derived from all three germ layers of tissues, including ectoderm, mesoderm and endoderm. More specifically, the present invention relates to the use of miR-302-like siRNA (siR-302) and/or miR-302 precursors (pre-miR-302) for developing novel medicines and therapies against a variety of human cancers, in particular lung cancers.

Abstract: The present invention concerns a method for treating a demyelinating condition in a subject, by administering an agent to the subject that inhibits vascular endothelial cell phagocytosis. The method of the invention is useful in treating, for example, a demyelinating condition associated with an injury, such as a spinal cord injury or traumatic brain injury, as well as other demyelinating conditions, such as multiple sclerosis.

Abstract: Accurate mapping of RNA-Seq reads to the reference genome is critical for accurate identification and quantification of miRNA transcripts. The miRNA transcriptome of two homozygous lymphoblastoic cell lines with completely characterized MHC haplotypes (PGF and COX) was analyzed and revealed 89 novel mature miRNA transcripts originating from within the MHC, including three mature miRNA that are haplotype specific, one of which originates from within intron 5 of HLA-DRB5. This is a novel way to identify miRNA transcripts originating from the MHC in a variety of tissue types and disease states, and can be utilized to prepare personal genome assemblies.

Abstract: The present invention provides a suppression type antisense oligonucleotide targeting TDP-43 mRNA, containing a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a nucleotide sequence shown in any of SEQ ID NOs: 2-4, and a promotion type antisense oligonucleotide targeting TDP-43 mRNA, containing a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a nucleotide sequence shown in SEQ ID NO: 5.

Abstract: The present disclosure provides compositions and methods for treating a disorder associated with mutations in the CEP290 gene. The disclosure includes synthetic polynucleotides for skipping a reading-frame of a CEP290 pre-RNA, yielding a CEP290 translated product that lacks one or more exons. The disclosure also provides methods of treating patients with the synthetic polynucleotides disclosed herein.

Abstract: The present invention provides VWF protective agents, including aptamers and antibodies for the treatment and or amelioration of complications or disorders arising from aberrant binding or function of VWF.

Abstract: The disclosure relates to the assembly of Virus Like Particles [VLPs] using packaging native and artificial packaging signals and their use in vaccines and immunological compositions and the methods of vaccination or immunisation against human and animal viral pathogens.

Abstract: Provided herein are immunotherapy compositions for treating a subject with a glioblastoma, comprising a peptide formulation derived from at least one cancer or sternness factor, nanoparticles containing peptides derived from at least one cancer or sternness factor, dendritic cells containing peptides derived from at least one cancer or sternness factors, RNA coding at least one cancer or sternness factor, nanoparticles containing RNA coding at least one cancer or sternness factor, dendritic cells containing RNA coding at least one cancer factor or sternness factor, or an inhibitor of at least one cancer or sternness factor. Also provided are methods of inhibiting a glioblastoma stem-like cell (GSC), methods of treating a subject for glioblastoma, and methods of reprogramming an astrocyte to a glioblastoma stem-like cell (GSC) using such immunotherapy compositions.

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: The invention relates methods of using RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1.

Abstract: Provided are methods for treatment of neuropathic pain. The method comprises providing to an individual in need of treatment an effective amount of miR-133b-3p miRNA and/or miR-143-3p miRNA, with or without miR-1a-3p miR-NA. Compositions comprising these miRNAs, their precursors of vectors encoding the miRNAs are also provided.

Abstract: This disclosure relates to novel targets for angiogenic disorders. Novel oligonucleotides are also provided. Methods of using the novel oligonucleotides for the treatment of angiogenic disorders (e.g., preeclampsia) are also provided.