Abstract: Rationally-designed LAGLIDADG meganucleases and methods of making such meganucleases are provided. In addition, methods are provided for using the meganucleases to generate recombinant cells and organisms having a desired DNA sequence inserted into a limited number of loci within the genome, as well as methods of gene therapy, for treatment of pathogenic infections, and for in vitro applications in diagnostics and research.

Abstract: The present invention concerns the endonucleases capable of cleaving a target sequence located in a “safe harbor loci”, i.e. a loci allowing safe expression of a transgene. The present invention further concerns the use of such endonucleases for inserting transgenes into a cell, tissue or individual.

Abstract: The present invention relates to a phytase which has at least 74% identity to a phytase derived from Citrobacter braakii and comprises at least one alteration as compared to this phytase. These phytase variants have amended, preferably improved, properties, such as thermostability, temperature profile, pH profile, specific activity, performance in animal feed, reduced protease sensitiliby, and/or an amended glycosylation pattern. The invention also relates to DNA encoding these phytases, methods of their production, as well as the use thereof, e.g. in animal feed and animal feed additives.

Abstract: Specified restriction endonucleases have been characterized for the first time by their amino acid and DNA sequences. These sequences and those with at least 90% identity thereto have been used as probes in sequence similarity analyses to identify sequence matches in a sequence database that corresponds to novel restriction endonucleases or isoschizomers. The sequence similarity analyses includes selecting a positive sequence match from any sequence producing an expectation value of less than or equal to e?02.

Abstract: The invention provides methods of manufacturing oils and oil-based products such as transportation fuels, industrial chemicals, edible oils, lubricants and plastics using sucrose feedstocks from sugar cane, sugar beets, and molasses for bioproduction processes. The disclosed processes utilize oleaginous microbes as a conversion technology to convert chemical energy produced by sugar cane, molasses and sugar beets into energy-containing oils and oil derivatives. Also provided herein are oleaginous microbes containing one or more exogenous sucrose utilization genes.

Abstract: The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a bicyclic compound. The present invention also relates to methods of using the compositions.

Abstract: The invention provides methods of cultivating oil-bearing microbes using xylose alone or in combination with other depolymerized cellulosic material. Also provided are microorganisms comprising an exogenous gene encoding a polysaccharide degrading enzyme, such as a cellulase, a hemicellulase, a pectinase, or a driselase. Some methods of microbial fermentation are provided that comprise the use of xylose and depolymerized cellulosic materials for the production of oil-bearing microorgansims.

Abstract: The present invention relates to a method of modifying a target sequence in the genome of a eukaryotic cell, the method comprising the step: (a) introducing into the cell a fusion protein comprising a DNA-binding domain of a Tal effector protein and a non-specific cleavage domain of a restriction nuclease or a nucleic acid molecule encoding the fusion protein in expressible form, wherein the fusion protein specifically binds within the target sequence and introduces a double strand break within the target sequence. The present invention further relates to the method of the invention, wherein the modification of the target sequence is by homologous recombination with a donor nucleic acid sequence further comprising the step: (b) introducing a nucleic acid molecule into the cell, wherein the nucleic acid molecule comprises the donor nucleic acid sequence and regions homologous to the target sequence.

Abstract: A method for performing homologous recombination between at least a first nucleic acid molecule and a second nucleic acid molecule which share at least one region of sequence homology. A method for improving the efficiency of homologous recombination.

Abstract: The present invention relates to phytases having at least 76% identity to a phytase derived from Hafnia alvei and comprises at least one modification in the amino acid sequence thereof. These phytase variants have modified, preferably improved, properties, such as, reduced protease sensibility, preferably they exhibit improved properties in respect of thermal performance, such as heat-stability (temperature stability, thermostability), steam stability, pelleting stability and/or temperature profile; and/or protease stability, in particular pepsin stability, pH profile, specific activity, substrate specificity, performance in animal feed (such as an improved release and/or degradation of phytate), susceptibility to glycation, and/or glycosylation pattern. The invention also relates to DNA encoding these phytases, methods of their production, as well as the use thereof, e.g., in animal feed and animal feed additives.

Abstract: Provided is a methylation-specific restriction endonuclease for a DNA duplex substrate, which endonuclease recognizes in a strand of the duplex a 2 to 6 nucleotide recognition sequence comprising a 5-methylcytosine, and cleaves each strand of the duplex at a fixed position outside the recognition sequence.

Abstract: The invention relates to the finding that T cell protein tyrosine phosphatase (TCPTP) has a tumour suppressor function. In one particular application, the invention provides a method of diagnosis and/or prognosis of cancer in a subject involving the assessment, in a suitable body sample, of any lack or reduction of TCPTP protein and/or Ptpn2 gene expression. The invention also provides a method of treating or preventing cancer in a subject involving administering to a subject an agent for modulating the activity of TCPTP.

Abstract: Methods and materials related to producing 3-HP as well as other organic compounds are disclosed. Specifically, isolated nucleic acids, polypeptides, host cells, and methods and materials for producing 3-HP and other organic compounds are disclosed.

Abstract: A process for efficiently producing optically active succinimide derivatives as key intermediates of (3R)-2?-(4-bromo-2-fluorobenzyl)spiro{pyrrolidine-3,4?(1?H)-pyrrolo[1,2-a]pyrazine}-1?,2,3?,5(2?H)-tetraone, which comprises the following reaction steps, and the step 2 is performed by using a non-animal-derived enzyme.

Abstract: Provided herein are methods and compositions for expressing a modified polypeptide in a host cell, wherein the modified polypeptide comprises a terminal mannose at an N-linked glycosylation site of the polypeptide. The methods and compositions used herein involve the use of RNA effector molecules (e.g., siRNA, dsRNA etc) administered to a host cell to modify the expression of target genes involved in protein glycosylation (e.g., Mgat1, Mgat4, SLC35A1, SLC35A2 or GNE).

Abstract: Described herein are methods and genetically engineered cells useful for producing an altered N-glycosylation form of a target molecule. Also described are methods and molecules with altered N-glycosylation useful for treating a variety of disorders such as metabolic disorders.

Abstract: The present invention is directed to targeting genes and genomes, modifying the activity of enzymes and protein expression in plants. In particular, the present invention relates to methods for reducing the activity of one or more endogenous glycosyltransferases such as N-acetylglucosaminyltransferase, ?(1,2)-xylosyltransferase and a(1,3)-fucosyl-transferase in a plant cell and to plants obtained by said method.

Abstract: The present invention concerns novel methods for improving cleavage of DNA by rare-cutting endonucleases, overcoming DNA modification constraints, particularly DNA methylation, thereby giving new tools for genome engineering, particularly to increase the integration efficiency of a transgene into a genome at a predetermined location, including therapeutic applications and cell line engineering.

Abstract: The present invention relates to an agent for use as a modulator of apoptosis-factor-associated cell death, apoptosis, cell survival, migration and/or proliferation, a method of diagnosing or monitoring apoptosis-factor-associated conditions or disorders as well as a method of identifying a modulator of apoptosis-factor-associated cell death, apoptosis, cell survival, migration and/or proliferation. Preferably, the invention relates to TRAIL-induced cell death and/or TRAIL-induced apoptosis. Preferably the agents are used to stimulate and/or enable TRAIL-induced cell death or to inhibit TRAIL-induced cell death. The preferable use of the diagnostic tools is to diagnose sensitivity or resistance to TRAIL-induced cell death or induction of sensitivity or resistance to TRAIL-induced cell death by an agent.

Abstract: The present disclosure provides a method for producing a Dicer polypeptide in a prokaryotic host cell. The present disclosure further provides a purified Dicer complex. The present disclosure further provides kits for producing a Dicer polypeptide in a prokaryotic host cell.

Abstract: The invention provides methods of manufacturing oils and oil-based products such as transportation fuels, industrial chemicals, lubricants and plastics using sugar cane, sugar cane juice, corn steep liquor, corn starch or depolymerized cellulosic material as a feedstock for bioproduction processes. Oils are manufactured using microalgae expressing sucrose invertase, which allows the microalgae to produce oil using sucrose-based feedstocks, along or in combination with other feedstocks.

Abstract: Compositions and methods are provided for enzymes with altered properties that involve a systematic approach to mutagenesis and a screening assay that permits selection of the desired proteins. Embodiments of the method are particularly suited for modifying specific properties of restriction endonucleases such as star activity. The compositions includes restriction endonucleases with reduced star activity as defined by an overall fidelity index improvement factor.

Abstract: The present invention relates to a method to improve the secretion of a protein of interest by a filamentous fungal cell comprising inducing a phenotype in the cell selected from the group consisting of a lowered ERAD, an elevated UPR that does not induce an elevated ERAD, wherein ERAD preferably is lowered. The invention further relates to the filamentous fungal cell comprising the phenotype described above. The invention also relates to polynucleotides and polypeptides whose expression can be modulated in the filamentous fungal cell to obtain the above-described phenotype.

Abstract: The present invention relates to methods for changing the state of differentiation of a eukaryotic cell, the methods comprising introducing mRNA encoding one or more reprogramming factors into a cell and maintaining the cell under conditions wherein the cell is viable and the mRNA that is introduced into the cell is expressed in sufficient amount and for sufficient time to generate a cell that exhibits a changed state of differentiation compared to the cell into which the mRNA was introduced, and compositions therefor. For example, the present invention provides mRNA molecules and methods for their use to reprogram human somatic cells into pluripotent stem cells.

Abstract: Meganuclease variants cleaving DNA target sequences of the NANOG gene, vectors encoding such variants, and cells expressing them. Methods of using meganuclease variants recognizing NANOG gene sequences for modifying the NANOG gene sequence or for incorporating a gene of interest or therapeutic gene using the NANOG gene as a landing pad and a safe harbor locus.

Abstract: The invention is based on the surprising finding that proteins regulated by excessive EGFR signalling in the liver may be used as biomarkers in the diagnosis, prognosis and/or monitoring of treatment of diseases, including liver cell dysplasia or hepatocellular carcinoma (HCC), wherein the protein is selected from a first group consisting of Arginase type II, 4931406C07Rik (Ester hydrolase C11orf54 homolog), Akr1c12 protein, Alanyl-tRNA synthetase, Aldo-keto reductase family 1 member C14, Aldo-keto reductase family 1 member C6, Aldolase 3, Alpha glucosidase 2, Beta 5-tubulin, Cai protein (Pdia4), cDNA sequence BC021917 (dihydroxyacetone kinase 2 homolog), Farnesyl diphosphate synthetase, Fatty acid binding protein 5 epidermal, Inosine triphosphatase, Interleukin 25, Kininogen 1, LIM and SH3 protein 1, Major vault protein, Nucb1 protein, Poly(rC) binding protein 2; heterogeneous nuclear ribonucleoprotein X, Psmd11 protein, RIKEN cDNA 2410004H02, Rps12 protein, Sars1 protein, Sorcin, T43799 proteasome protein p

Abstract: The invention relates to meganuclease variants which cleave a DNA target sequence from the human Rhodopsin gene (RHO), to vectors encoding such variants, to a cell, an animal or a plant modified by such vectors and to the use of these meganuclease variants and products derived therefrom for genome therapy, ex vivo (gene cell therapy) and genome engineering including therapeutic applications and cell line engineering.

Abstract: A heat labile alkaline phosphatase enzyme and methods of using the same and kits including the same are disclosed. Specifically, a nucleotide sequence of, peptide sequence of, methods of using, and kits comprising, a heat labile alkaline phosphatase isolated from Colwellia psychrerythraea are provided. Methods of over-expression and purification of the recombinant alkaline phosphatase and mutants thereof are also disclosed. Methods of over-expressing and purifying commercially useful quantities of active recombinant heat labile alkaline phosphatase fusion enzymes from C. psychrerythraea, wherein the fusion enzymes comprise one or more heterologous leader sequences are disclosed. The disclosed C. psychrerythraea heat labile alkaline phosphatase has properties similar to shrimp alkaline phosphatase and can be substituted for shrimp alkaline phosphatase in assays involving the same.

Abstract: The present disclosure is generally directed to glycosyl hydrolase enzymes, compositions comprising such enzymes, and methods of using the enzymes and compositions, for example for the saccharification of cellulosic and hemicellulosic materials into sugars.

Abstract: The invention provides methods of manufacturing oils and oil-based products such as transportation fuels, industrial chemicals, edible oils, lubricants and plastics using sugar cane, sugar beets, and cane/beet agricultural processing byproducts as a feedstock for bioproduction processes. The disclosed processes utilize oil-bearing microbes as a conversion technology to convert chemical energy produced by sugar cane and sugar beets into energy-containing oils and oil derivatives. Also provided herein are oil-bearing microbes containing one or more exogenous sucrose utilization genes.

Abstract: The invention provides a process and kit for serial isolation of DNA and RNA from the same sample. First, a siliceous solid support with preferential affinity for DNA over RNA is used to capture DNA in a lysate of a sample. Next, a siliceous solid support with similar affinity for RNA and DNA is used to capture RNA from the same lysate. The respective solid supports are recovered independent of each other, washed, and their bound nucleotide species are eluted. The invention further provides DNA and RNA prepared using the process in a minimal number of steps employing a minimal number of reagents. As the invention yields DNA and RNA of high quality and is amenable to automation, the invention may be used widely in the healthcare and pharmaceutical industries.

Abstract: A method for the secretory production of a glycoprotein having a human-type sugar chain, comprising a step of introducing a gene of an enzyme capable of performing a transfer reaction of a galactose residue to a non-reducing terminal acetylglucosamine residue, and a gene of heterologous glycoprotein, to obtain a transformed plant cell, a step of culturing the plant cell, and a step of recovering the culture medium of the plant cell.

Abstract: The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a quinone compound. The present invention also relates to methods of using the compositions.

Abstract: The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a dioxy compound. The present invention also relates to methods of using the compositions.

Abstract: The present invention relates to compositions and methods useful for analyzing lariat RNA, which plays a role in the regulation of gene expression. A sample of RNA is specifically treated to remove linear mRNA and enrich for lariat RNA. The enriched lariat RNA sample may be analyzed further to identify introns, branch point sequences, alternative splicing patters, and gene transcription levels. The enriched lariat RNA sample may also be exploited as a detection or compound screening tool, as well as other uses.

Abstract: Nucleases and methods of using these nucleases for alteration of a CFTR gene and generation of cells and animal models.

Abstract: The invention relates to meganuclease variants which cleave a DNA target sequence from the human dystrophin gene (DMD), to vectors encoding such variants, to a cell, an animal or a plant modified by such vectors and to the use of these meganuclease variants and products derived therefrom for genome therapy, ex vivo (gene cell therapy) and genome engineering including therapeutic applications and cell line engineering. The invention also relates to the use of meganuclease variants for inserting therapeutic transgenes other than DMD at the dystrophin gene locus, using this locus as a safe harbor locus. The invention also relates to the use of meganuclease variants for using the dystrophin gene locus as a landing pad to insert and express genes of interest.

Abstract: The present invention relates to a method of producing a heterologous protein or polypeptide having phytase activity in a yeast system. The invention also provides proteins having phytase activity which have increased thermostability. Yeast strains which produce a heterologous phytase and the vectors used to produce the phytase are also provided.

Abstract: The present invention relates to enzymes and processes. In particular, there is described an isolated polypeptide comprising the amino acid sequence corresponding to Citrobacter freundii phytase or a homologue, a modified form, a functional equivalent or an effective fragment thereof. There is also described a host cell transformed or transfected with a nucleic acid encoding a bacterial phytase enzyme or a modified form as well as the use of such a phytase or modified form in food or animal feed.

Abstract: The present invention provides methods and kits for editing specific chromosomal sequences in cells. In particular, targeting endonucleases and single-stranded nucleic acids are used to edit the chromosomal sequence.

Abstract: A biomarker, method, test kit, and diagnostic system for detecting the presence of lymphoma in a person are disclosed. The lymphoma may be Hodgkin's lymphoma or non-Hodgkin's lymphoma. The person may be a high-risk subject. In one embodiment, a plasma sample from a person is obtained. The level of at least one protein listed in Table S3 in the plasma sample is measured. The level of at least one protein in the plasma sample is compared with the level in a normal or healthy subject. The lymphoma is diagnosed based upon the level of the at least one protein in the plasma sample in comparison to the normal or healthy level.

Abstract: The invention relates to Citrobacter phytases derived from Citrobacter amalonaticus, Citrobacter gillenii, and related phytases. The phytases belong to the acid histidine phosphatase family, are acid-stable, and expectedly of a high specific activity. The invention also relates to the corresponding DNA, the recombinant and wild-type production of the phytases, as well as the use thereof, in particular in animal feed.

Abstract: An acetyl xylan esterase variant having perhydrolytic activity is provided for producing peroxycarboxylic acids from carboxylic acid esters and a source of peroxygen. More specifically, a Thermotoga maritima acetyl xylan esterase gene was modified using error-prone PCR and site-directed mutagenesis to create an enzyme catalyst characterized by an increase in specific activity. The variant acetyl xylan esterase may be used to produce peroxycarboxylic acids suitable for use in a variety of applications such as cleaning, disinfecting, sanitizing, bleaching, wood pulp processing, and paper pulp processing applications.

Abstract: The present disclosure provides variant Csy4 endoribonucleases, nucleic acids encoding the variant Csy4 endoribonucleases, and host cells genetically modified with the nucleic acids. The variant Csy4 endoribonucleases find use in a variety of applications, which are also provided. The present disclosure also provides methods of detecting a specific sequence in a target polyribonucleotide; and methods of regulating production of a target RNA in a eukaryotic cell.

Abstract: Methods are provided for making restriction endonucleases with reduced star activity by one or more targeted mutations to a catalytic site within the restriction endonuclease. Examples of modifications to restriction endonucleases with significant sequence identity with KpnI are provided and reduced star activity demonstrated.

Abstract: Compositions and methods are provided for enzymes with altered properties that involve a systematic approach to mutagenesis and a screening assay that permits selection of the desired proteins. Embodiments of the method are particularly suited for modifying specific properties of restriction endonucleases such as star activity. The compositions includes restriction endonucleases with reduced star activity as defined by an overall fidelity index improvement factor.

Abstract: Disclosed are methods of making and using engineered FokI cleavage domain variants. Also disclosed are methods, compositions and fusion proteins containing obligate heterodimers of engineered FokI cleavage domain variants and DNA binding domains, such as zinc finger protein (ZFP) domains and transcription activator-like effector (TALE) domains.

Abstract: An antimicrobial activity enhancing agent for lactoferrin or a lactoferrin hydrolysate, which contains a milk protein as an active ingredient and has the following properties, and a method for producing the antimicrobial activity enhancing agent, which comprises (a) the step of contacting raw milk with a cation exchange resin to adsorb proteins in the raw milk to the cation exchange resin, (b) the step of washing the cation exchange resin having undergone the adsorption treatment, and flowing an elution solvent to elute a protein fraction having an isoelectric point of 9.0 to 11.0, and (c) the step of subjecting the eluted protein fraction to membrane filtration using an ultrafiltration membrane having a molecular weight cutoff of 30 kDa to prepare the milk protein having the following properties: (A) an action of enhancing the antimicrobial activity of lactoferrin or a lactoferrin hydrolysate, (B) a molecular weight of 30 kDa or less, (C) an isoelectric point of 9.0 to 11.0.

Abstract: Disclosed are rationally-designed, non-naturally-occurring meganucleases in which a pair of enzyme subunits having specificity for different recognition sequence half-sites are joined into a single polypeptide to form a functional heterodimer with a non-palindromic recognition sequence. The invention also relates to methods of producing such meganucleases, and methods of producing recombinant nucleic acids and organisms using such meganucleases.

Abstract: An acetyl xylan esterase variant having perhydrolytic activity is provided for producing peroxycarboxylic acids from carboxylic acid esters and a source of peroxygen. More specifically, a Thermotoga maritima acetyl xylan esterase gene was modified using error-prone PCR and site-directed mutagenesis to create an enzyme catalyst characterized by an increase in specific activity. The variant acetyl xylan esterase may be used to produce peroxycarboxylic acids suitable for use in a variety of applications such as cleaning, disinfecting, sanitizing, bleaching, wood pulp processing, and paper pulp processing applications.