Abstract: Targeted transcriptional effectors (transcription activators and transcription repressors) derived from meganucleases are described. Also described are nucleic acids encoding same, and methods of using same to regulate gene expression. The targeted transcriptional effectors can comprise (i) a meganuclease DNA-binding domain lacking endonuclease cleavage activity that binds to a target recognition site; and (ii) a transcription effector domain.

Abstract: The present disclosure provides improved genome editing compositions and methods for editing a CBLB gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

Abstract: Chimeric and other variant ?-glucuronidase enzymes with enhanced properties as compared to unmodified enzyme are provided. The enzymes of the invention advantageously exhibit enhanced enzymatic activity, enhanced substrate range, enhanced pH range, enhanced temperature range and/or enhanced enzyme stability. Methods of using the variant enzymes for hydrolysis of glucuronide substrates, including opiates and benzodiazepines, are also provided.

Abstract: Polypeptides, and methods for their use, are disclosed that have an amino acid sequence at least 75% identical to the amino acid sequence of SEQ ID NO:1, are provided, wherein (a) the polypeptide degrades a PFQPQLPY (SEQ ID NO: 140) peptide and/or a PFPQPQQPF (SEQ ID NO: 68) at pH 4; (b) residue 467 is Ser, residue 267 is Glu, and residue 271 is Asp; and (c) the polypeptide comprises an amino acid change from SEQ ID NO: 1 at one or more residues selected from the group consisting of 221, 262E, 268, 269, 270, 319A, 320, 354E/Q/R/Y, 358S/Q/T, 368F/Q, 399, 402, 406, 424, 449, 461, 463, 105, 171, 172, 173, 174, and 456.

Abstract: Disclosed is a method for recovering a desired fermentation product from a fermentation broth where the desired product has precipitated during the fermentation.

Abstract: The present invention relates to novel subtilase variants exhibiting increased stability and preferably on par or improved wash performance. The variants of the invention are suitable for use in e.g. cleaning or detergent compositions, such as laundry detergent compositions and dish wash compositions, including automatic dish wash compositions. The present invention also relates to isolated DNA sequences encoding the variants, expression vectors, host cells, and methods for producing and using the variants of the invention.

Abstract: The present invention provides a method for improving or controlling the plasma half-life and/or bio-availability of blood coagulation factor IX (FIX), the method comprising modifying the GLA domain. Examples of such modifications include: (i) non-covalent bonding of a GLA-domain-recognizing antibody or an antibody fragment thereof to the GLA domain; (ii) reduced number of Gla residues in the GLA domain, in comparison to that of a native FIX; (iii) either or both of deletion of one or more glutamic acid residues in the GLA domain and substitution of one or more glutamic acid residues in the GLA domain with another amino acid; and (iv) deletion of a part or all of the GLA domain. The present invention also provides a FIX with improved pharmacokinetics which carries such modifications, a pharmaceutical composition containing the FIX as an active ingredient, a method for producing the FIX, and such.

Abstract: An arginine deiminase mutant with improved enzyme activity and temperature stability and application thereof were provided, belonging to the technical field of genetic engineering and enzyme engineering. The arginine deiminase mutant is proline, namely Gly292 Pro, mutated from glycine near an enzyme active center. A wild-type arginine deiminase arcA coding gene is molecularly modified by a site-directed mutation technique to obtain a mutant enzyme ADIG292P, which has glycine at position 292 of an amino acid sequence of the wild type arginine deiminase mutated to proline. The arginine deiminase, modified by site-directed mutation, of the present invention has 1.5 times of increase in enzyme activity and 5.43 times of increase in half-life period at 40° C.

Abstract: A protein construct including a gene encoding a light-sensitive protein fused to at least one of either a low complexity sequence, an intrinsically disordered protein region (IDR), or a repeating sequence of a linker and another gene encoding a light-sensitive protein. Among the many different possibilities contemplated, the protein construct may also advantageously include cleavage tags. This protein construct may be utilized for a variety of functions, including a method for protein purification, which requires introducing the protein construct into a living cell, and inducing the formation of clusters by irradiating the construct with light. The method may also advantageously include cleaving a target protein from an IDR, and separating the clusters via centrifuge. A kit for practicing in vivo aggregation or liquid-liquid phase separation is also included, the kit including the protein construct and a light source capable of producing a wavelength that the light-sensitive protein will respond to.

Abstract: The present disclosure relates to compositions, systems, and methods for the production of biomolecules using microorganisms. In particular, the present disclosure provides biomolecule production platforms that include genetically engineered microorganisms with genetic circuits functionally coupled to microcapsules formed from materials that are responsive to culture conditions. The biomolecule production platforms disclosed herein facilitate the efficient and robust production, purification, and/or analysis of any biomolecule-of-interest.

Abstract: The invention generally relates to compositions and methods for isolating circulating cells. In one aspect, the invention provides a method for isolating one or more target cells in a biological fluid of a subject, the method comprising: selectively providing to the one or more target cells an effective amount of at least one iron saccharide complex or a pharmaceutically acceptable derivative thereof; and isolating the target cells using a magnetic source capable of generating a magnetic field effective to capture target cells containing a magnetically responsive intracellular concentration of the of at least one iron saccharide complex or a pharmaceutically acceptable derivative thereof in the magnetic field. In further aspects, the method can comprise treating the target cell will one or more cancer treatments. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Disclosed herein are microbial defense systems, which provide cells protection against phage infection and plasmid transformation. Methods of use of these defense systems for protecting cells from phage infection and plasmid transformation are also disclosed, wherein defense systems may be used individually or in combination. In addition, disclosed herein are methods of making cells that express these defense systems.

Abstract: Methods are provided for reducing the complexity of a population of nucleic acids prior to performing an analysis of the nucleic acids, e.g., sequence analysis. The methods result in a subset of the initial population enriched for a target region, which is typically located within one or more target fragments. The methods are particularly useful for analyzing populations having a high degree of complexity, e.g., chromosomal-derived DNA, whole genomic DNA, or mRNA populations.

Abstract: The present disclosure provides a kit for preparing a library of nucleic acids. The kit includes first and second oligonucleotide, each having a tail sequence, a common sequence, and at least one of a unique identifier sequence, and a variable length punctuation mark. The kit further includes a first primer having a first sample identifier sequence and a first priming sequence at a 3? end of the first primer. The first priming sequence includes the tail sequence of the first oligonucleotide. The kit further includes a second primer having a second sample identifier sequence and a second priming sequence at a 3? end of the second primer. The second priming sequence is complimentary to the second tail sequence of the second oligonucleotide.

Abstract: Methods and compositions for modulating a target genome are disclosed.

Abstract: The invention provides improved gene therapy vectors, compositions, and methods.

Abstract: Disclosed herein are methods for inhibiting or activating the transcription of a gene of interest, or inhibiting or activating the transcription of specific mRNA isoforms of a gene by using antisense oligonucleotides and/or small molecules. Also described herein are methods for activating transcription from a promoter and increasing overall gene expression by creating of a new splice site in a gene of a cell.

Abstract: Provided herein are RNAi molecules including a first strand containing a guide sequence and a second strand comprising a non-guide sequence where the non-guide sequence contains a bulge opposite the seed region of the guide sequences; e.g., opposite the cleavage sequence. In some aspects, the invention provides RNAi for treating Huntington's disease. Further provided herein are expression cassettes, vectors (e.g., rAAV, recombinant adenoviral, recombinant lentiviral, and recombinant HSV vectors), cells, viral particles, and pharmaceutical compositions containing the RNAi. Yet further provided herein are methods and kits related to the use of the RNAi, for example, to treat Huntington's disease.

Abstract: Inhibitory nucleic acids, e.g., antisense oligonucleotides (ASO) against PAR-TERRA RNA or other chromosome-specific TERRA transcripts (i.e., inclusive of chromosome-specific subtelomeric sequences), and methods of use thereof to downregulate expression of escapee genes on the inactive X chromosome, expression from the active X chromosome, subtelomeric autosomal loci (e.g., FSHD locus), or expression of autosomal genes involved in growth control and apoptosis, e.g., in cells and subjects with supernumerary X chromosomes and/or cancer and other human diseases.

Abstract: This invention provides a method for the in vivo delivery of oligonucleotides. The invention utilizes the presence of one or plurality of HES linked to an oligonucleotide to deliver a nucleic acid sequence of interest into the cytoplasm of cells and tissues of live organisms. The delivery vehicle is nontoxic to cells and organisms. Since delivery is sequence-independent and crosses membranes in a receptor-independent manner, the delivered oligonucleotide can target complementary sequences in the cytoplasm as well as in the nucleus of live cells. Sequences of bacterial or viral origin can also be targeted. The method can be used for delivery of genes coding for expression of specific proteins, antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNAs or any nucleic acid sequence in a living organism. The latter include mammals, plants, and microorganisms such as bacteria, protozoa, and viruses.

Abstract: Disclosed herein are compositions and methods for inhibiting the growth of cells or inducing cell death. The composition capable of inhibiting the growth of cells or inducing cell death comprises a 5?-triphosphate non-linear RNA. The RNA comprises a first stem-loop formed from the complete or partial hybridization of at least 8 nucleotide pairings and may optionally comprise a second stem-loop formed from the complete or partial hybridization of at least 8 nucleotide pairings and a spacer between the first stem-loop and the second stem loop. Methods for inhibiting the growth of cells or inducing cell death comprise contacting cells with the composition or administering the composition to a subject in an amount effective to inhibit the growth of the cells or induce death of the cells.

Abstract: In certain aspects, provided herein are RNA complexes (e.g., asymmetric RNA complexes, such as asiRNAs or cell penetrating asiRNAs) that inhibit IL4R?, TRPA1, and/or F2RL1 expression and are therefore useful for treating atopic dermatitis or asthma.

Abstract: Genetic modulators comprising two or more artificial transcription factors for use in specific and active modulation of gene expression are provided.

Abstract: The disclosure provides methods of making a tetracycline inducible expression system in a cell. The methods include providing the cell with a first nucleic acid sequence comprising a first promoter operably linked to a tetracycline repressor gene coding sequence, providing the cell with a second nucleic acid sequence comprising a second promoter operably linked to a coding sequence of a gene of interest wherein the second promoter is modified to include one or more tetracycline repressor protein binding sites, and determining the expression of the gene of interest in the presence or absence of tetracycline. The disclosure further provides nucleic acid sequences, vectors and cells including the tetracycline inducible modified promoter.

Abstract: Nucleic acid constructs for use in a method of selecting cells comprising a genome editing event, the method comprising (a) transforming cells of a plant of interest with the nucleic acid construct; (b) selecting transformed cells exhibiting fluorescence emitted by the fluorescent reporter using flow cytometry or imaging; and (c) culturing the transformed cells comprising the genome editing event by the DNA editing agent for a time sufficient to lose expression of the DNA editing agent so as to obtain cells which comprise a genome editing event generated by the DNA editing agent but lack DNA encoding the DNA editing agent.

Abstract: This disclosure pertains to a novel platform for genetic engineering of chloroplasts. The disclosure provides episomal DNA vectors containing a chloroplast origin of replication. These vectors remain extra-plastomic and sustainably and autonomously replicate in chloroplasts of the plant cells transformed with the vectors and in the plants regenerated from the transformed plant cells. The episomal DNA vectors do not contain any sequence that shares sequence homology with the plastome DNA and, thus, do not get integrated into the plastome DNA. The vectors can also comprise one or more genes of interest that confer desirable characteristics to the transformed plant cells. The disclosure also provides methods of transforming plant cells with the episomal DNA vectors and regenerating from the transformed plant cells plants having desirable characteristics.

Abstract: This invention relates to methods of controlling gene expression or gene suppression in eukaryotic cells. One aspect of this invention includes modifying the degree of silencing of a target gene by use of a modified suppression element. Another aspect includes providing a eukaryotic cell having a desired phenotype resulting from transcription in the eukaryotic cell of a modified suppression element. Also provided are transgenic eukaryotic cells, transgenic plant cells, plants, and seeds containing modified suppression elements, and useful derivatives of such transgenic plant cells, plants, or seeds, such as food or feed products.

Abstract: Provided are isolated polypeptides which are at least 80% homologous to SEQ ID NOs: 202-219, 221-292, 295-327, 4064-4175, 4177-4210, 4212-4580, 4582-4603, 4605-4749, 4751-4778, 4780-5223, 5225-5493, 5522-5807, 5812, 5815-5816, 5828-6679, 6689-6690, 6708-6785, 6792-6892 or 6893, isolated polynucleotides which are at least 80% identical to SEQ ID NOs: 1-91, 94-201, 328-2317, 2320-2321, 2323, 2326-3835, 3838-3840, 3842-3843, 3848, 3850-3852, 3854, 3856-3953, 3955-4061 or 4062, nucleic acid constructs comprising same, transgenic cells expressing same, transgenic plants expressing same and method of using same for increasing yield, abiotic stress tolerance, growth rate, biomass, vigor, oil content, photosynthetic capacity, seed yield, fiber yield, fiber quality, fiber length, and/or nitrogen use efficiency of a plant.

Abstract: Methods and materials for modulating cold tolerance levels in plants are disclosed. For example, nucleic acids encoding cold tolerance-modulating polypeptides are disclosed as well as methods for using such nucleic acids to transform plant cells. Also disclosed are plants having increased levels of cold tolerance and plant products produced from plants having increased cold tolerance levels.

Abstract: The present invention is directed to controlling pest infestation by inhibiting one or more biological functions in an invertebrate pest. The invention discloses methods and compositions for use in controlling pest infestation by feeding one or more different recombinant double stranded RNA molecules to the pest in order to achieve a reduction in pest infestation through suppression of gene expression. The invention is also directed to methods for making transgenic plants that express the double stranded RNA molecules, and to particular combinations of transgenic pesticidal agents for use in protecting plants from pest infestation.

Abstract: This invention is direct to methods of switching from sexual reproduction to apomixis or from apomixis to sexual reproduction in a eukaryote. More particularly this invention provides methods of switching from meiosis to apomeiosis and from syagamy to parthenogenesis in a plant. The invention also provides methods of producing an apomictic eukaryote from a sexual eukaryote and a sexual eukaryote from an apomietic eukaryote.

Abstract: The present invention provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which lack expression of functional endogenous immunoglobulin loci. The present invention also provides ungulate animals, tissue and organs as well as cells and cell lines derived from such animals, tissue and organs, which express xenogenous, such as human, immunoglobulin loci. The present invention further provides ungulate, such as porcine genomic DNA sequence of porcine heavy and light chain immunogobulins. Such animals, tissues, organs and cells can be used in research and medical therapy. In addition, methods are provided to prepare such animals, organs, tissues, and cells.

Abstract: In certain embodiments an optimized derivative of the CCLc-?AS3-FB lentiviral vector termed (CCLc-mGata/ANK-CoreLCR-?AS3-FB), is provided which is capable of driving lineage-restricted expression of a beta-globin gene (e.g., an anti-sickling ?-globin like gene (?A83)). In certain embodiments the vectors described herein comprise novel defined LCR HS core sequences (HS2(˜420 bp), HS3?40 bp), HS4(˜410 bp)) which can be used to replace the putative LCR HS sequences present within the “mini-LCR” (˜3.6 kb reduced to ˜1.2 kb) to produce an “optimized mini-LCR”.

Abstract: The present invention relates generally to immunization and immunotherapy for the treatment or prevention of HIV. In particular, the methods include in vivo and/or ex vivo enrichment of HIV-specific CD4+ T cells.

Abstract: The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises capsid protein VP1, wherein said capsid protein VP1 is from one or more than one first AAV serotype, wherein said capsid protein VP2 is from one or more than one first AAV serotype and capsid protein VP3, wherein said capsid protein VP3 is from one or more than one second AAV serotype and wherein at least one of said first AAV serotype is different from at least one of said second AAV serotype and is different from at least one of said third AAV serotype, in any combination.

Abstract: Provided nucleic acid-based expression construct for the target cell-specific production of a therapeutic protein, such as a pro-apoptotic protein, within a target cell, including a target cell that is associated with aging, disease, or other condition, in particular a target cell that is a senescent cell or a cancer cell.

Abstract: This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering nucleic acids in vivo. These compositions have reduced immune activation resulting in accelerated blood clearance and/or anti-drug antibodies and they have an improved toxicity profile and therapeutic index in vivo.

Abstract: Disclosed herein are methods of genome alteration, in particular genome editing in eukaryotic cells (e.g., mammalian cells), preferably, but not exclusively the integration of exogenous nucleic acids into the genome of a cell or a population of cells. Such methods include the modulation of cell cycle phases via external conditions such as physical separation, temperature, exposure to certain substances such as cell cycle modulators. Genome alteration is also effected via the use of enzymes such as nucleases and nickases and/or the modulation of DNA repair pathways.

Abstract: Provided herein are precise gene replacement methods and transgenic non-human animals produced by such methods, in which an endogenous non-human animal gene of interest is precisely replaced with a human syntenic gene. The resulting genetically modified non-human animals are useful for evaluating molecular impact of pathogenic mutations within the context of the human genomic sequence in which they occur in patients and for screening for potential therapeutic agents.

Abstract: Provided is a method for producing PHA by a microbe with improved productivity of PHA, and a PHA-producing microbe used for the production method. A method for producing polyhydroxyalkanoic acid, the method including a step of culturing a microbe having a polyhydroxyalkanoic acid synthase gene and an inactivated gene encoding a flagellar protein to cause the microbe to produce polyhydroxyalkanoic acid. In the microbe, a lipase, a dephosphorylating enzyme, and a protein represented by the amino acid sequence of SEQ ID NO: 6 or 7 may be additionally inactivated. The microbe may be Cupriavidus necator.

Abstract: The disclosure discloses recombinant Pseudomonas plecoglossicida for producing L-xylose and application thereof, and belongs to the technical field of bioengineering. According to the disclosure, a synthesized 2-ketogluconate reductase gene and a 2,5-diketogluconate reductase gene derived from Corynebaterium ATCC 31090 and a pyruvate decarboxylase gene derived from Saccharomyces cerevisiae are successfully expressed in a host P. plecoglossicida by a double plasmid system, and an obtained genetically engineered strain is fermented for 56 h in a shake flask, where the yield of L-xylose reaches 16.2 g/L, and the transformation rate reaches 20.3%; the obtained genetically engineered strain is fermented for 48 h and 44 h in 3 L and 15 L fermentors, respectively, where the yields of L-xylose reach 37.6 g/L and 45.8 g/L, respectively, and the glucose transformation rates are 47.0% and 57.3%, respectively.

Abstract: Methods and compositions for capping RNA in an in vitro transcription mixture are provided that include a thermostable RNA polymerase variant and a cap analog such that when a DNA template is added to the mixture, and the mixture is then incubated under conditions for in vitro transcription, capped RNA is produced.

Abstract: The present disclosure provides, in some embodiments, methods and compositions for exponential amplification of single- and double-stranded DNA under isothermal conditions.

Abstract: Compositions, methods and kits are disclosed for synthesizing and amplifying pools of probes using precursor oligonucleotides. In some aspects the precursor is amplified and nicking enzymes are used to separate the full length probes from the amplification products. The methods enable the preparation of single stranded DNA probes of defined sequence and length that are suitable for use in target detection assays.

Abstract: A process of fermentation of starch-containing cereal materials, such as a process of producing high protein biomass from starch-containing cereal materials by yeast strains, includes following steps: producing glucose for use as a substrate from starch-containing cereal materials by liquefaction and saccharification; selecting yeast strains which produce high protein biomass and storing the selected yeast strains; and producing high protein biomass from yeast strains by using the glucose produced, optionally in combination with molasses. The produced high protein biomass is useful in animal husbandry, especially for pig, aquatic, poultry, and large-scale animal husbandry on an industrial scale. The produced high protein biomass can replace antibiotics in the livestock industry, thereby reducing imports of products from abroad.

Abstract: Provided herein, in one aspect, is a composition for in vitro transcription and translation, comprising: a treated cell lysate derived from one or more organisms such as bacteria, archaea, plant or animal; a plurality of supplements for gene expression; an energy recycling system for providing adenosine triphosphate and recycling adenosine diphosphate; and an engineered propeptide operably linked to a stabilizing domain. Methods for making and using the same are also provided.

Abstract: Disclosed herein are compositions for assessing peptidoglycan biosynthesis in bacteria, for identifying bacteria, and for screening for bacterial cell wall-acting and/or cell wall-disrupting agents via modified D-amino acids and methods of use thereof. Also disclosed are live bacteria having one or more modified D-amino acids as described herein incorporated into peptidoglycan of a bacterial cell wall.

Abstract: A device for differentially enumerating colonies of coliform and Escherichia coli microorganisms is provided. The device comprises a water-impermeable first sheet; a water-impermeable second sheet attached to the first sheet; a dry, rehydratable culture medium comprising a lactose-fermentation indicator system, a ?-D-glucuronidase indicator system that comprises a plurality of compounds that enhance ?-glucuronidase enzyme activity in E. coli, a redox indicator system and a first cold-water soluble gelling agent adhered to the first sheet, the culture medium disposed in a microbial growth zone; and a second cold-water-soluble gelling agent adhered to the second sheet. The microbial growth zone is disposed between the first sheet and the second sheet. Methods of using the device are also provided.

Abstract: The present disclosure relates to methods of evaluating, identifying, and/or producing (e.g., manufacturing) pharmaceutical products (e.g., protein therapeutics). In some instances, methods herein allow highly resolved evaluation of the disulfide bond profiles of protein therapeutics.

Abstract: The present invention is related to a method for evaluation of drug efficacy of a medicine having a therapeutic or preventive effect against a disease related to EL activity wherein phosphatidylinositol or lysophosphatidylinositol is used as an indicator. The present invention is also related to a method for screening an inhibitor of EL activity using phosphatidylinositol and a kit for use in the method.