Abstract: Provided herein are methods and composition for immune repertoire sequencing and single cell barcoding. The methods and compositions can be used to heavy and light chain antibody sequences originating from a single cell, antibody discovery, disease and immune diagnostics, and low error sequencing.

Abstract: Described is a method for screening an encoded chemical library, which library comprises a plurality of different chemical structures each releasably linked to an encoding tag, the method comprising the steps of: (a) providing said library of tagged chemical structures; (b) releasing each chemical structure from its tag to produce a plurality of free, tagless chemical structures (TCSs); (c) screening the TCSs by contacting them with a assay system under conditions whereby a spatial association between each TCS and its tag is maintained, to produce a plurality of different screened TCSs each spatially associated with its tag; and (d) identifying a screened TCS by decoding a tag that is spatially associated therewith.

Abstract: The present invention relates to the method of rational design for generic antisense oligonucleotide libraries for genome-wide screening, particularly in the research area for antisense pharmaceutical lead discovery and validation. The libraries are being constructed systematically. The building block is antisense codon. The present invention is aimed at overcoming the drawbacks of both oligonucleotide libraries constructed according to algorithm of 4.sup.n and randomized libraries at the same time. It is applicable for all cells, tissues, organs and organisms with necessary judgments.

Abstract: Disclosed herein are compositions and methods for construction of chromatin immunoprecipitation (ChIP) sequencing libraries involving the use of Tn5 tagmentation, splint ligation and/or single-stranded DNA ligation.

Abstract: A functional engineered guide RNA sequence is provided including a spacer sequence and a scaffold sequence, wherein the scaffold sequence includes a primer binding site for reverse transcription.

Abstract: The present invention relates to agents, compositions and methods for inhibiting the expression of a target gene, comprising an RNAi agent bearing at least one galactosyl moiety. These are useful for delivering the gene expression inhibiting activity to cells, particularly hepatocytes, and more particularly in therapeutic applications.

Abstract: Disclosed herein are compositions and methods for reducing expression of C9ORF72 mRNA and protein in an animal. Such methods are useful to treat, prevent, ameliorate, or slow progression of neurodegenerative diseases in an individual in need thereof.

Abstract: Reagents and methods to cloak and uncloak RNA polymers and applications thereof are provided. Photocloaking molecules are used to label RNA polymers. Radiant energy is used to remove photoreleaseable protecting adducts and revert a RNA polymer to its native form.

Abstract: In certain embodiments, the present invention provides the use of microRNA (miR)-200a to inhibit ossification and bone formation.

Abstract: This application relates to therapeutic siRNA agents and methods of making and using the agents.

Abstract: The present disclosure describes improved SELEX methods for producing aptamers that are capable of binding to target molecules and improved photoSELEX methods for producing photoreactive aptamers that are capable of both binding and covalently crosslinking to target molecules. Specifically, the present disclosure describes methods for producing aptamers and photoaptamers having slower dissociation rate constants than are obtained using prior SELEX and photoSELEX methods. The disclosure further describes aptamers and photoaptamers having slower dissociation rate constants than those obtained using prior methods. In addition, the disclosure describes aptamer constructs that include a variety of functionalities, including a cleavable element, a detection element, and a capture or immobilization element.

Abstract: The present invention discloses small plant virus RNA molecules involved in modulating a plant defence response, particularly non-translated, plant viral microRNA molecules. The present invention also provides methods of their production and uses of these microRNA molecules for reducing a susceptibility of a plant to a pathogen.

Abstract: Provided are 9-base morpholino antisense compounds targeted to polyCUG repeats in the 3?UTR region of dystrophia myotonica protein kinase (DMPK) mRNA, and related methods for treating myotonic dystrophy DM1.

Abstract: Disclosed herein include compositions and methods of modulating protein expression that utilizes an activator or a repressor of a non-sense mediated RNA decay switch exon (NSE). In some embodiments, also included herein are compositions and methods of modulating protein expression that uses an agent that targets a transposed element.

Abstract: Therapeutic compositions and methods of treatment of the central nervous system, specifically towards hypertension comprising administration of a therapeutic comprising an anti-miR-135a, an anti-miR-miR-376a, or a combination, in the central nervous system effectively attenuates hypertension for up to four weeks provided a single administration.

Abstract: Methods of expressing an expression product of interest are provided. Accordingly there is provided a method comprising introducing into a cell a polynucleotide comprising an AimR responsive element operatively linked to a nucleic acid sequence encoding the expression product of interest, and contacting said cell with an AimP peptide comprising an amino acid sequence of XXXXGG/A, wherein said AimP peptide is capable of binding said AimR polypeptide and dissociating said AimR polypeptide from said AimR responsive element. Also provided are articles of manufacture, isolated peptides, polynucleotides and nucleic acid constructs.

Abstract: The present invention relates to methods of enhancing the translation ability and stability of an RNA molecule. The methods involve providing a cell-free composition comprising an RNA molecule to be translated, where the RNA molecule lacks an N6,2?O-dimethyladenosine (“m6Am”) residue. Also disclosed are methods of making RNA molecules and treatment methods using an RNA molecule comprising a 7-methylguanosine (“m7G”), a 5? triphosphate linker (“-ppp-”), and an N6,2?-0-dimethyladenosine (m6Am).

Abstract: The present disclosure relates to a polypeptide having an acyltransferase activity or a microorganism including the same; a composition for preparing N-acetyl-L-methionine, the composition including the polypeptide or microorganism; and a method of preparing N-acetyl-L-methionine using the polypeptide or microorganism. Further, the present disclosure relates to a polynucleotide encoding the polypeptide and an expression vector including the polynucleotide. Since the microorganism including a novel acyltransferase according to the present disclosure has enhanced acyltransferase activity, this microorganism can be efficiently used for producing N-acetyl-L-methionine by acetylating L-methionine.

Abstract: Fungal artificial chromosome (FAC) vectors are disclosed. A vector can be replicated in a bacterial or a fungal host, and can comprise an insert of heterologous DNA up to about 500 kilobases. A vector can be used for cloning and expressing a secondary metabolite (SM) gene cluster. An insert sequence can be modified by homologous recombination. A vector can be a plasmid comprising bacterial and fungal origins of replication, as well as bacterial and fungal selection marker genes. Also disclosed are vectors that can be integrated into a fungal genome, and dual function vectors which can be replicated in a bacterial or a fungal host and can also be integrated into a fungal genome. Also disclosed are methods of generating plasmid libraries including vectors comprising intact SM gene clusters.

Abstract: The present invention relates to a yeast cell, in particular a recombinant yeast cell, the cell lacking enzymatic activity needed for the NADH-dependent glycerol synthesis or the cell having a reduced enzymatic activity with respect to the NADH-dependent glycerol synthesis compared to its corresponding wild-type yeast cell, the cell comprising one or more heterologous nucleic acid sequences encoding an NAD+-dependent acetylating acetaldehyde dehydrogenase (EC 1.2.1.10) activity. The invention further relates to the use of a cell according to the invention in the preparation of ethanol.

Abstract: Disclosed herein are compositions and methods for effecting alterations at a defined location in the genome of a non-epidermal plant cell. Further disclosed are methods for providing plants having a modified phenotype or a modified genome.

Abstract: The invention provides to improved methods for the modification of genes in plant cells, and plants and seeds derived therefrom. More specifically, the invention relates to the increased efficiency of targeted gene mutation by combining gene repair oligonucleotides with approaches that enhance the availability of components of the target cell gene repair mechanisms.

Abstract: Materials and methods are provided for making plants with altered levels of amino acids, particularly by making controlled frameshift mutations in genes that are highly expressed in plant leaves or plant seeds.

Abstract: Transgenic host cells, vectors useful for making transgenic host cells, and kits useful for making transgenic host cells are described. Also described are transgenic plants. In some embodiments, transgenic host cells express a 4-hydroxyphenylacetaldehyde synthase (4HPAAS). In some embodiments, transgenic host cells express a tyrosol:UDP-glucose 8-O-glucosyltransferase (T8GT). The transgenic host cells are useful for biosynthesis of one or more of salidroside, icariside D2, tyrosol, and 4-hydroxypenylacetaldehyde.

Abstract: Provided are novel polynucleotide compositions for enhancing the herbicidal activity of glyphosate. Specifically provided are methods and compositions for modulating 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) in plant species. The present compositions and methods are useful in controlling glyphosate resistant weeds.

Abstract: The invention relates to a method of enhancing the potency of a cell (for example, to a totipotent state), by introducing a TET family gene, derivative or fragment thereof into the cell. The invention also relates to methods and kits for preparing cells with enhanced potency, and uses of said cells.

Abstract: Virus vectors wherein each of the virus vectors expresses a sequence targeting a consensus conserved nucleic acid sequence, which when expressed in cells, functions as a modulator for nucleic acid encoding a domain.

Abstract: The invention provides a bidirectional hCMV-CAG4 promoter and recombinant vectors and recombinant virus comprising the bidirectional hCMV-CAG4 promoter operably linked to a first transgene in one direction and to a second transgene in the opposite direction. The invention also provides methods of making and using such recombinant vectors and recombinant virus.

Abstract: A non-integrating viral delivery system is disclosed. The system includes a viral carrier, wherein the viral carrier contains a defective integrase gene; a heterologous viral episomal origin of replication; a sequence encoding at least one initiator protein specific for the heterologous viral episomal origin of replication, wherein expression of the sequence encoding the at least one initiator protein specific for the heterologous viral episomal origin of DNA replication is inducible; and at least one gene, gene product, shRNA, siRNA, miRNA, or other RNA of interest.

Abstract: This invention relates generally to populations of microvesicles containing or otherwise associated with viral particles, methods of producing these purified populations, and methods of using these purified populations in a variety of diagnostic, therapeutic and/or prophylactic indications.

Abstract: A transfection method for inserting nucleic acids into eukaryotic cells using a non-viral gene delivery system is provided, the cells being treated at least with at least one inhibitor for IKKe and/or TBK1 and at least one inhibitor for nucleic-acid-detecting toll-like receptors before and/or during the transfection, and a composition and a toolkit system for a method of this type.

Abstract: There is provided an attachment configured to detachably couple to a fluid extruding device, the attachment comprising: a membrane having a plurality of pores configured to allow a cell to pass through while inducing a mechanical stress to the cell such that the introduction of one or more substances into the cell is facilitated; and an engaging member for coupling to the outlet of the fluid extruding device such that the membrane is in fluid communication with the outlet of the fluid extruding device, wherein the fluid extruding device is configured to extrude fluid via mechanical actuation.

Abstract: New cationic lipids are provided that are useful for delivering macromolecules, such as nucleic acids, into eukaryotic cells. The lipids can be used alone, in combination with other lipids and/or in combination with other transfection enhancing reagents to prepare transfection complexes.

Abstract: Described herein are methods and vectors for rational, multiplexed manipulation of chromosomes within open reading frames (e.g., in protein libraries) or any segment of a chromosome in a cell or population of cells, in which various CRISPR systems are used.

Abstract: Compositions and methods are provided for novel Cas9 orthologs, including, but not limiting to, novel guide polynucleotide/Cas9 endonucleases complexes, single or dual guide RNAs, guide RNA elements, and Cas9 endonucleases. The present disclosure also describes methods for creating a double strand break in a target polynucleotide, methods for genome modification of a target sequence under various in vivo and in vitro conditions, in the genome of a cell, for gene editing, and for inserting a polynucleotide of interest into the genome of a cell. Also provided are nucleic acid constructs and cells having a modified target site or altered polynucleotide of interest produced by the methods described herein.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: Mutations involving amino acid substitution were introduced into various sites of diphosphomevalonate decarboxylase (MVD), thus preparing a large number of MVD variants. Then, the variants were each evaluated in terms of a catalytic activity for production of olefin compounds such as isoprene. As a result, it was found that substitution of glycine at position with a different amino acid resulted in improvement in the catalytic activity. In addition, it was found that the MVD in which arginine at position and threonine at position in addition to the position were further substituted with different amino acids, respectively, also had the high catalytic activity.

Abstract: Microorganisms that co-consume glucose with non-glucose carbohydrates, such as xylose, and methods of using same. The microorganisms comprise modifications that reduce or ablate the activity of a phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS) protein or modifications that reduce or ablate the activity of a phosphoglucose isomerase and a GntR. The PTS protein may be selected from an enzyme I (EI), an HPr, an FPr, and an enzyme IIGlc (EIIGlc). Additional modifications include reduction or ablation of the activity of a pyruvate formate lyase, a lactate dehydrogenase, and a fumarate reductase and inclusion of recombinant pyruvate decarboxylase and alcohol dehydrogenase genes. The microorganisms are particularly suited to co-consuming glucose and xylose in media containing these substrates and producing ethanol therefrom.

Abstract: The disclosure provides a metabolic pathway for producing a metabolite, the metabolic pathway having a co-factor regulatory system for cofactor utilization in the metabolic pathway.

Abstract: The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO), 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway comprising at least one exogenous nucleic acid encoding a BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine pathway enzyme expressed in a sufficient amount to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine and further optimized for expression of BDO. The invention additionally provides methods of using such microbial organisms to produce BDO, 4-hydroxybutyryl-CoA, 4-hydroxybutanal or putrescine.

Abstract: This document describes biochemical pathways for producing 1,3-butanediol using a polypetide having ?-ketothiolase activity to form a 3-oxo-5-hydroxypentanoyl-CoA intermediate that can be enzymatically converted to 1,3-butanediol, as well as recombinant hosts producing 1,3-butanediol.

Abstract: A non-naturally occurring microbial organism includes a microbial organism having a reductive TCA or Wood-Ljungdahl pathway in which at least one exogenous nucleic acid encoding these pathway enzymes is expressed in a sufficient amount to enhance carbon flux through acetyl-CoA. A method for enhancing carbon flux through acetyl-CoA includes culturing theses non-naturally occurring microbial organisms under conditions and for a sufficient period of time to produce a product having acetyl-CoA as a building block. Another non-naturally occurring microbial organism includes at least one exogenous nucleic acid encoding an enzyme expressed in a sufficient amount to enhance the availability of reducing equivalents in the presence of carbon monoxide or hydrogen, thereby increasing the yield of redox-limited products via carbohydrate-based carbon feedstock.

Abstract: Provided herein are compositions and methods for production of organic acids. In particular, provided herein are consolidated bioprocessing compositions and methods for single reactor production of organic acids.

Abstract: The present invention provides a method for reducing the content of phospholipids in a phospholipid-containing oil material by converting the phospholipids into fatty acid alkyl esters (FAAE) and free fatty acids (FFA). The method comprises reacting a phospholipid-containing oil material with one or more phospholipases in a system comprising a low content of a short chain alcohol and water. The method can be used in degumming or as an enzymatic pretreatment before transesterification and/or biodiesel production, but it can also be used as basic oleochemical in further downstream processes of the oleochemical industry. The present invention also provides a method for producing free fatty alkyl esters (FAAE) from phospholipids in a phospholipid containing oil material by reacting the phospholipids with one or more phospholipases in a reaction mixture comprising a low content of a short chain alcohol and water.

Abstract: The present invention relates to a compound of general formula I The present invention also relates to a method of producing N-acetyl homoserine and/or derivatives thereof, the method comprising contacting at least one recombinant cell in an aqueous medium with acetate wherein the recombinant cell comprises an increased activity relative to a wild type cell of (a) an enzyme E1, a homoserine dehydrogenase (EC1.1.1.3) and/or an enzyme E5, an aspartokinase (EC2.7.2.4); and (b) an enzyme E2, a homoserine O-acetyl transferase (EC2.3.1.31) and the acetate is maintained at a concentration of at least about 0.001 g/L in the aqueous medium.

Abstract: Methods for propagation of yeast using cellulosic material as a carbon source are disclosed. A propagation medium is provided by combining a nutrient source, a cellulosic material to be used as a carbon source, enzymes that hydrolyze the cellulosic material into monosaccharides that can be taken up and metabolized by yeast, and a first cell mass of yeast. The propagation medium is incubated in a temperature range that allows the enzymes to break down the cellulosic material into monosaccharides at a rate that leads to production of a second cell mass of yeast, while keeping ethanol production low enough that the concentration of ethanol does not exceed 0.1 grams per liter of propagation medium.

Abstract: Reaction compositions are disclosed herein comprising at least water, beta-glucose-1-phosphate (beta-G1P), an acceptor molecule, and an alpha-1,3-glucan phosphorylase enzyme. These reactions can synthesize oligosaccharides and polysaccharides with alpha-1,3 glycosidic linkages. Further disclosed are alpha-1,3-glucan phosphorylase enzymes and methods of use thereof.