Abstract: Described herein is a chemostat-like continuous cell culture system that combines certain advantages of perfusion open systems and chemostat open systems to improve the culturing of mammalian cells, e.g., genetically modified cells, particularly in serum-free or chemically-defined media. The continuous culture system described herein involves culturing mammalian cells in a continuous cell culture system, which comprises a cell retention device, wherein the cell culture system has a dilution rate (D) of less than about 2 d?1, and a cell density of less than about 2×107 cell/mL.

Abstract: This invention provides a range of translatable messenger UNA (mUNA) molecules. The mUNA molecules can be translated in vitro and in vivo to provide an active polypeptide or protein, or to provide an immunization agent or vaccine component. The mUNA molecules can be used as an active agent to express an active polypeptide or protein in cells or subjects. Among other things, the mUNA molecules are useful in methods for treating rare diseases.

Abstract: A mutant Bacillus subtilis, which does not express a functional KASIIIA and/or KASIIIB, and method of making; a mutant Rhodospirillum rubrum, which does not express a functional PhaC1, PhaC2, and/or PhaC3, and method of making; method of characterizing substrate specificity of KASIII; method of making mutant KASIII with altered substrate specificity and/or altered level of activity and nucleic acid, vector, host cell/organism, and mutant KASIII; an in vitro, high-throughput spectrophotometric method of assaying KASIII activity; and materials and methods for using KASIII for production of bi-functional fatty acids and the materials so produced.

Abstract: The present invention relates to a new isolated polypeptide comprising an amino acid sequence having at least 75%, 80%, 85%, 90%, 95%, 99% or 100% identity to the full length amino acid sequence set forth in SEQ ID NO:1, and having a polyester degrading activity, and uses thereof.

Abstract: Transposase polypeptides and polynucleotides are provided, which have a high activity in mammalian cells. Methods for engineering cells, such as chimeric antigen T-cells, with the transposes are also provided.

Abstract: Materials and methods related to gene targeting (e.g., gene targeting with transcription activator-like effector nucleases; “TALENS”) are provided.

Abstract: Materials and methods related to gene targeting (e.g., gene targeting with transcription activator-like effector nucleases; “TALENS”) are provided.

Abstract: The present invention relates to variants (mutants) of polypeptides, in particular Termamyl-like alpha-amylases, which variant has alpha-amylase activity and exhibits an alteration in at least one of the following properties relative to said parent alpha-amylase: substrate specificity, substrate binding, substrate cleavage pattern, thermal stability, pH/activity profile, pH/stability profile, stability towards oxidation, Ca2+ dependency, specific activity, in particular laundry and dish-wash applications.

Abstract: The present invention provides variant subtilisins and compositions comprising at least one variant subtilisin set forth herein, as well as methods for using these variants and compositions. In some embodiments, the present invention provides variant subtilisins suitable for laundry cleaning applications.

Abstract: Heparinases SDhep I and SDhep II obtained from a bacterium Sphingobacterium daejeonense are heparin enzymes that have not been reported. The enzymes were obtained by steps of bacterium fermentation, crude enzyme extraction, multi-step column chromatography and so on. A study in properties showed that the two enzymes are specific for enzymolysis of heparin and are expected to be used in low molecular weight heparins preparation or heparin quality testing.

Abstract: An enzyme-polymer conjugate shows increased activity and molecular dissolution in non-aqueous solvents enabling enzyme mediated catalysis in non-aqueous solutions. The inventions described in this specification relate to enzyme-polymer conjugates, organic solutions comprising enzyme-polymer conjugates, methods of dissolving enzyme-polymer conjugates in organic solvents, and methods of using enzyme-polymer conjugates, for example, in catalysis applications. The inventions described in this specification address the problems of insolubility and decreased activity of enzymes in non-aqueous solutions comprising, for example, organic solvents or ionic liquids.

Abstract: The present invention provides a highly active protease that can be used in sample preparation for mass spectrometry of a protein and has excellent stability against a change in an external environment. The present invention provides an immobilized protease characterized in that a crudely purified protease or a protease that has not been subjected to a self-digestion resistance treatment is immobilized on surfaces of nanoparticles, and provides a method for producing the immobilized protease. The immobilized protease of the present invention can maintain high activity without being subjected to a change in an external environment, and thus is effective, for example, in preparing a sample to be supplied for mass spectrometry of a protein in a clinical specimen.

Abstract: A portable device for extracting DNA from a sample comprising a tissue with a plurality of cells. The device includes an opening configured to receive the sample, a first region in fluid communication with the opening and comprising a plurality of tissue processing elements; a second region having a first dehydrated buffer configured to change a first characteristic of the sample and cause lysis of at least some of the plurality of cells in the sample; a third region having a second dehydrated buffer configured to prevent at least some of a plurality of proteins in the sample from progressing from said third region to the fourth region; a fourth region having a third dehydrated buffer configured to purify the DNA from said sample; and an exit designed to allow for the purified DNA to exit the device.

Abstract: A method of collecting a nucleic acid(s) from a biological sample includes step a) mixing an aluminum oxide support with a water-soluble neutral polymer adsorbed on a surface thereof and a solution containing a nucleic acid(s), thereby adsorbing the nucleic acid(s) to the support; step b) separating the support on which the nucleic acid(s) is/are adsorbed from the solution mixed in step a); and step c) collecting the nucleic acid(s) by adding an eluent to the support on which the nucleic acid(s) is/are adsorbed and which is separated in step b).

Abstract: The invention relates to methods of purifying viral vectors from cell culture. In particular, the invention relates to a method of purifying a supernatant containing viral vectors from a cell culture, comprising removing cells by filtering said cell culture using diatomaceous earth.

Abstract: The present invention relates to methods for displaying cyclic peptides on the surface of bacteriophage particles and collections thereof.

Abstract: Described herein are approaches for the improved detection, identification, and/or quantification of target nucleic acids. These approaches provide a means of detecting, identifying, and/or quantifying rare target nucleic acid molecules, including DNA and RNA molecules, from the same sample, and in the same reaction, by using “hairpin barcode primers,” as the term is defined herein, to incorporate unique barcodes into target nucleic acids in a PCR pre-amplification step.

Abstract: Disclosed herein are methods for the generation of nucleic acid libraries encoding for gRNA sequences. The gRNAs encoded by methods described herein may be single or double gRNA sequences. Methods described provide for the generation of gRNA libraries, as a DNA precursor or as a RNA transcription product, with improved accuracy and uniformity.

Abstract: The present disclosure provides methods and systems for identifying biologically active random peptides (BARPs) in plants. The present disclosure also provides libraries of transformed plants, where each plant expresses a different candidate BARP. Also provided are engineered, isolated BARPs capable of producing a non-wild type phenotype in plants.

Abstract: The present invention provides materials and methods useful for error correction of nucleic acid molecules. In one embodiment of the invention, a first plurality of double-stranded nucleic acid molecules having a nucleotide mismatch are fragmented by exposure to a molecule having unidirectional mismatch endonuclease activity. The nucleic acid molecules are cut at the mismatch site or near the mismatch site, leaving a double-stranded nucleic acid molecule having a mismatch at the end or near end of the molecule. The nucleic acid molecule is then exposed to a molecule having unidirectional exonuclease activity to remove the mismatched nucleotide. The missing nucleotides can then be filled in by the action of, e.g., a molecule having DNA polymerase activity. The result is double-stranded nucleic acid molecules with a decreased frequency of nucleotide mismatches.

Abstract: The present invention relates to modified guide RNAs and their use in clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems.

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: Disclosed are methods for modulating splicing of Tau mRNA in an animal with Tau antisense compounds. Also disclosed herein are methods for reducing expression of Tau mRNA and protein in an animal with Tau antisense compounds. Such compounds and methods are useful to treat, prevent, or ameliorate neurodegenerative diseases in an individual in need thereof. Examples of neurodegenerative diseases that can be treated, prevented, and ameliorated with the administration Tau antisense oligonucleotides include Alzheimer's Disease, Fronto-temporal Dementia (FTD), FTDP-17, Progressive Supranuclear Palsy, Chronic Traumatic Encephalopathy, Epilepsy, and Dravet's Syndrome.

Abstract: The present invention refers to inhibitors of the miR-17-92 cluster and to their use as medicaments, in particular in the treatment of multiple myeloma and other malignancies. More in particular, the present invention refers to an LNA/DNA gapmer which binds to a region of the primary miRNA (pri-miRNA) of the miR-17-92 cluster Said inhibitors can be used for the treatment of tumors related to an overexpression of any of the miRNAs of the miR-17-92 cluster. Pharmaceutical compositions are also within the scope of the invention.

Abstract: The present invention provides a compound represented by the formula (Ia) as a novel cationic lipid that forms a lipid particle and also provides a lipid particle comprising the compound. The present invention further provides a nucleic acid lipid particle containing the lipid particle, and a pharmaceutical composition containing the nucleic acid lipid particle as an active ingredient.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Delta-like 1 homolog (DLK1), in particular, by targeting natural antisense polynucleotides of Delta-like 1 homolog (DLK1). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of DLK1.

Abstract: The application discloses methods and compositions for the inhibition of the alternative complement pathway. The methods and compositions involve the use of aptamers for inhibiting complement Factor D. The application further provides anti-Factor D aptamers for the treatment of dry age-related macular degeneration, geographic atrophy, wet age-related macular degeneration or Stargardt disease.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of filovirus infections. In particular, the present invention relates to a method of treating filovirus infection in a subject in need thereof comprising administering the subject with a therapeutically effective amount of at least one oligonucleotide comprising the sequence as set forth in SEQ ID NO:1 to SEQ ID NO:15.

Abstract: A method of treating a condition in a mammal comprising administering a pharmacologically effective amount of a therapeutic, wherein the therapeutic one of increases EphA2 expression and supplements ephrin type-A receptor 2, and the condition is one of fatty liver disease, elevated plasma cholesterol level, and elevated plasma triglyceride level.

Abstract: Methods and compositions are disclosed for controlling expression of TNF receptors (TNFR1 and TNFR2) and of other receptors in the TNFR superfamily using compounds that modulate splicing of pre-mRNA encoding these receptors. More specifically these compounds cause the removal of the transmembrane domains of these receptors and produce soluble forms of the receptor which act as an antagonist to reduce TNF-? activity or activity of the relevant ligand. Reducing TNF-? activity provides a method of treating or ameliorating inflammatory diseases or conditions associated with TNF-? activity. Similarly, diseases associated with other ligands can be treated in like manner. In particular, the compounds of the invention are splice-splice switching oligomers (SSOs) which are small molecules that are stable in vivo, hybridize to the RNA in a sequence specific manner and, in conjunction with their target, are not degraded by RNAse H.

Abstract: The present invention relates to a mutant organism having the ability to produce aspartic acid derivatives, wherein a gene encoding the glyoxylate shunt regulator and a gene encoding fumarase are deleted and a gene encoding aspartase is overexpressed compared to that in a wild-type strain, and to a method for producing L-aspartic acid derivatives using the same. According to the present invention, various aspartic acid derivatives, including L-alanine, 3-aminopropionic acid, threonine, 1,3-diaminopropane, lysine, methionine, 3-hydroxypropionic acid, cadaverine, 5-aminovaleric acid, etc., can be produced by biological methods.

Abstract: The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

Abstract: Described herein are mutant cyanobacterial cell populations that have a smaller mean cell length than wild type cyanobacterial cell populations of the same species.

Abstract: Disclosed are genetically engineered organisms, such as yeast and bacteria, that have the ability to metabolize atypical nitrogen sources, such as melamine and cyanamide. Fermentation methods using the genetically engineered organisms are also described. The methods of the invention are robust processes for the industrial bioproduction of a variety of compounds, including commodities, fine chemicals, and pharmaceuticals.

Abstract: The present disclosure provides compositions and methods for altering gibberellin (GA) content in corn or other cereal plants. Methods and compositions are also provided for altering the expression of genes related to gibberellin biosynthesis through suppression, mutagenesis and/or editing of specific subtypes of GA20 or GA3 oxidase genes. Modified plant cells and plants having a suppression element or mutation reducing the expression or activity of a GA oxidase gene are further provided comprising reduced gibberellin levels and improved characteristics, such as reduced plant height and increased lodging resistance, but without off-types.

Abstract: Provided are compositions and methods relating to gene and/or protein mutations in plants. In certain embodiments, the disclosure relates to mutations in the allene oxide synthase 2 gene (i.e., AOS2). In some embodiments the disclosure relates to plants that are pathogen resistant.

Abstract: Compositions, systems and methods are provided for conferring disease resistance to plant pathogens that use proteases to target plant substrate proteins inside plant cells. Briefly, the compositions, systems and methods are based upon plant substrate proteins that are targeted by pathogen-specific proteases and that activate nucleotide binding site-leucine rich repeat (NB-LRR) disease resistance proteins when cleaved by the protease. These substrate proteins are modified such that the endogenous protease recognition sequence is replaced by a protease recognition sequence specific to a different pathogen protease (i.e., a heterologous protease recognition sequence). The modified plant substrate protein therefore can be used in connection with its corresponding NB-LRR protein to activate resistance in response to cleavage by the heterologous pathogen-specific protease. When activated by the plant pathogen-specific protease, the pair initiates host defense responses thereto, including programmed cell death.

Abstract: Methods, uses, and animals for introgression of alleles between animals, including SNPs. One embodiment involves introducing a targeted targeting endonuclease system and a HDR template into a cell with a mismatch in the binding of the targeting endonuclease and the targeted site.

Abstract: The present invention provides compositions and methods of use pertaining to rAAV-mediated delivery of therapeutically effective molecules for treatment of diseases such as Pompe disease. These compositions in combination with various routes and methods of administration result in targeted expression of therapeutic molecules in specific organs, tissues and cells.

Abstract: The teachings herein are generally directed to a method of enhancing the genetic stability of parvovirus vectors. The stability of conventional ss or dsAAV vector constructs can be enhanced, for example, to obtain a concurrent increase in vector titer and purity, as well as an improvement in vector safety, due at least in part to the elimination of stuffer DNA from the AAV vector. The method is broadly applicable to all gene transfer/therapy applications, such as those requiring delivery of foreign DNA containing recombinant gene expression cassettes. Such foreign DNA can range, for example, from about 0.2 up to about 5.2 kb in length. The enhanced vector constructs are highly flexible, user-friendly, and can be easily modified (via routine DNA cloning) and utilized (via standard AAV vector technology) by anyone skilled in the art.

Abstract: Disclosed are compositions and methods relating to the cardiac conduction system. Compositions, methods for converting cardiac tissue to an induced-sinoatrial node, and methods for treating sinus node dysfunction (SND) in an individual in need thereof are disclosed. Also disclosed are compositions and methods for evaluating virally-transduced cardiac tissue.

Abstract: A bis-alkoxyl amide alkyl cationic peptide lipid has a chemical structure as below: wherein the bis-alkoxyl amide alkyl cationic peptide lipid is dispersed in water to obtain the cationic peptide liposome which are high in stability and uniform in dispersion and have about 120 nm of average grain diameter and Zeta electric potential between 30 and 50 mV. The liposome can effectively compress the plasmids DNA and siRNA, can efficient transfection both in-vitro and in-vivo, and almost does not have toxicity to cells and mice, so that the liposome can be widely applied in gene delivery as a gene vector.

Abstract: It discloses a transformant for weight loss and lipid reduction, which is obtained by recombining and substituting human oxyntomodulin gene into thymidylate synthase gene of L. lactis genome. Wherein the recombinant substitution is homologous recombination by artificially synthesizing gene sequences, making the sequence flanking the human oxyntomodulin gene derived from the homologous sequences of thymidylate synthase gene in the L. lactis genome, then the gene fragments are electroporated into L. lactis, to carry out homologous recombination.

Abstract: A method for producing a composition containing a DHA-containing glyceride, including a step of obtaining a composition containing a DHA-containing glyceride, in which an esterification reaction is conducted by reacting a lipase with a raw material oil and fat containing highly unsaturated fatty acid as a constituent fatty acid in the presence of water and a lower alcohol to give a composition containing a DHA-containing glyceride, wherein a reaction liquid in the reaction has a water content of 0.4% by mass or more, and wherein the composition containing a DHA-containing glyceride has an acid value of 12 or less.

Abstract: The present invention is in the area of enzymes for (hemi-)cellulose degradation and/or modification, more in particular the degradation and/or modification of xylan. The invention is based on a newly discovered enzymatic activity of a class of lytic polysaccharide monooxygenases (LPMOs), i.e. oxidative cleavage of xylan in addition to oxidative cleavage of cellulose. The present invention therefore relates to a method for degrading and/or modifying xylan in a xylan-comprising substrate, a method for preparing a product from a xylan-comprising substrate, a kit of parts, a liquid, paste or solid formulation, and a xylan-comprising composition, comprising said LPMO. The invention further relates to a use of said LPMO, said kit of parts, said formulation and/or said composition, in a method of the invention.

Abstract: The invention relates to processes of closing an observed gap in sugar yield between pure batch hydrolysis and a multi-stage hydrolysis containing a continuous reactor. Enzyme compositions containing varied ratios of cellulolytic composition and a hemicellulolytic composition preconditioning are used in multi-stage hydrolysis processes containing a continuous reactor in order to close the gap. Such enzyme compositions are useful in multi-stage saccharification of a lignocellulosic material, fermentation processes following multi-stage saccharification of a lignocellulosic material and in improving a glucose or xylose yield in multi-stage saccharification of a lignocellulosic material.

Abstract: In the course of the present invention, it was discovered that one could regulate association between polypeptides by modifying amino acid residues that form the interface during the association to amino acids carrying the same type of charge. In this context, the present invention enables efficient formation of heterologous molecules. For example, the present invention can be suitably applied to the preparation of bispecific antibodies.

Abstract: A method of producing a device includes providing a substrate which has a recess. A multitude of loose particles is introduced into the recess. A first portion of the particles is coated by using a coating process having a depth of penetration which extends from an opening of the recess, along a direction of depth, and into the recess, so that the first portion is connected to form a solidified porous structure. The depth of penetration of the coating process which extends into the recess is set such that a second portion of the particles is not connected by means of the coating, and such that the solidified first portion of the particles is arranged between the second portion of the particles and surroundings of the recess. According to the invention, the second portion of the particles is at least partly removed from the recess.

Abstract: The present disclosure describes methods for detecting, monitoring, and modulating (e.g., promoting, enhancing, sustaining, maintaining, reducing, mitigating or eliminating of) biofilm formation, as well as mitigating or eliminating Microbial Influenced Corrosion (MIC) of a metal surface. The method of monitoring includes: providing a test sample; detecting at least one of a prophage gene, a prophage gene expression, a prophage gene transcript, a prophage protein, a prophage metabolite, a prophage intermediate, or a combination thereof, wherein the existence, amount or level of prophage gene expression, a prophage gene transcript, a prophage protein, a prophage metabolite, a prophage intermediate, or a combination thereof relative to a control is indicative of biofilm presence, formation or the state of the biofilm in a sample. The present disclosure also describes a composition for modulating biofilm formation, maintenance, mitigation, reduction, and elimination.

Abstract: A microfabricated device defining a high density array of microwells is described for cultivating cells from a sample. The device may be incubated to grow a plurality of cells, which may be split into an analysis portion and a reserve portion. Methods are provided for screening a biological entity of interest using the microfabricated device, for example, for screening phosphate solubilizing bacteria or other bacteria producing acids.