Abstract: A composition comprising a polycationic agent and a polyanionic agent, and kits comprising the composition, is provided. In embodiments, the polyanionic agent is a nucleic acid and the polycationic agent is a modified polyalkyleneimine polymer.

Abstract: The application provides a Diketoreductase (DKR) mutant, its nucleotide coding sequence, and an expression cassette, recombinant vector and host cell containing the sequence, as well as a method for application of the mutant to the preparation of 3R,5S-dicarbonyl compound. An ee value of the obtained 3R,5S-dicarbonyl compound is higher than 99%, and a de value is about 90%. The DKR mutant is a key pharmaceutical intermediate, and particularly provides an efficient catalyst for synthesis of a chiral dicarbonyl hexanoic acid chain of a statin drug.

Abstract: The invention relates to an isolated polypeptide with an glycosyl transferase enzymatic activity for producing dextrans with .alpha.(1.fwdarw.2) sidechains, comprising at least one region for bonding to glucan and a catalytically active region situated beyond the region bonding to glucan. The invention further relates to polynucleotides coding for said enzymes and vectors containing the same.

Abstract: Some aspects of this disclosure provide methods and compositions for the treatment of cancer, for example, head and neck cancer, in a subject using ALK1 inhibitors, e.g., ALK1-ECD polypeptides, ALK1-Fc fusion proteins, or ALK1-inhibitory antibodies. In some embodiments, methods and compositions are provided for treating certain cancers with ALK1 inhibitors in combination with a chemotherapeutic platinum agent. In some embodiments, methods are provided for identifying whether a cancer in a subject will react to treatment with an ALK1 antagonist, either alone or in combination with a chemotherapeutic platinum agent, for example, based on a determination that the cancer or the subject is positive for human papilloma virus.

Abstract: The invention relates to an expression system comprising a prokaryotic cell which contains a polynucleotide construct that encodes a T7 RNA polymerase under the control of a T7 promoter and under the control of an inducible promoter. The invention also relates to an expression vector which contains a gene that encodes a protein to be expressed under the control of a T7 promoter, characterized in that said expression vector comprises a plasmid stabilization system.

Abstract: Compositions that include polymerases with features for improving entry of nucleotide analogues into active site regions and for coordinating with the nucleotide analogues in the active site region are provided. Methods of making the polymerases and of using the polymerases in sequencing and DNA replication and amplification as well as kinetic models of polymerase activity and computer-implemented methods of using the models are also provided.

Abstract: This disclosure provides, among other things, a composition comprising: comprising a fusion protein comprising: (a) a DNA polymerase; and (b) a heterologous sequence-specific DNA binding domain. A method for copying a DNA template, as well as a kit for performing the same, are also described.

Abstract: This disclosure provides, among other things, a composition comprising: comprising a fusion protein comprising: (a) a DNA polymerase; and (b) a heterologous sequence-specific DNA binding domain. A method for copying a DNA template, as well as a kit for performing the same, are also described.

Abstract: The present invention relates to a lipase variant of a parent lipase, which variant has lipase activity, at least 75% but less than 100% sequence identity to SEQ ID NO: 3 and comprises a substitution at one or more positions corresponding to positions 1; 2; 3; 4; 5; 6; 7; 9; 10; 11; 12; 16; 19; 30; 31; 34; 36; 37; 39; 40; 42; 44; 51; 52; 53; 54; 56; 58; 59; 70; 71; 72; 73; 83; 84; 86; 88; 90; 92; 93; 95; 96; 100; 101; 102; 104; 106; 109; 110; 112; 117; 119; 124; 125; 127; 128; 131; 132; 133; 134; 135; 137; 158; 159; 160; 161; 162; 163; 165; 166; 167; 168; 170; 181; 182; 183; 189; 190; 192; 194; 196; 202; 210; 211; 212; 220; 225; 227; 228; 229; 230; 231; 233; 237; 238; 239; 240; 242; 246; 247; 248; 252; 259; 262; 264; 269 of SEQ ID NO: 3. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

Abstract: A novel TAL-effector nuclease (TALEN) for targeted knockout of the HIV co-receptor CCR5. One aspect provides a TAL-effector nuclease pair with a first and a second TAL-effector nuclease monomer, each TAL-effector nuclease monomer having an endonuclease domain having type II endonuclease activity and a TAL-effector DNA binding domain having a plurality of repeat units, each with a variable amino acid pair RVD, and wherein a) the TAL-effector DNA binding domain of the first TAL-effector nuclease monomer binds to the target sequence GCTGGTCATCCTCATCCTG (SEQ ID NO: 1) and/or comprises the RVD sequence NH HD NG NH NH NG HD NI NG HD HD NG HD NI NG HD HD NG NN, and b) the TAL-effector DNA binding domain of the second TAL-effector nuclease monomer binds to the target sequence AGATGTCAGTCATGCTCTT (SEQ ID NO: 2) and/or comprises the RVD sequence NI NN NI NG NN NG HD NI NH NG HD NI NG NH HD NG HD NG NG.

Abstract: The present invention relates to the expression and optimisation of enzymes involved in the breakdown of lignocellulosic biomass. The present invention specifically relates to variants of the exoglucanase 1 of Trichoderma reesei, as well as to the use of said variants with improved efficiency in methods for breaking down cellulose and for producing biofuel.

Abstract: The present invention relates to the expression and optimisation of enzymes involved in the breakdown of lignocellulosic biomass. The present invention specially relates to variants of the exoglucanase 2 of Trichoderma reesei, as well as to the use of said variants with improved efficiency in methods for breaking down cellulose and for producing biofuel.

Abstract: A method of generating a protein with an improved functional property, the method comprising: (a) identifying at least one Target amino acid Residue in a first protein, wherein said Target amino acid Residue is associated with said functional property; (b) comparing at least one homologous second protein from the same or a different phylogenetic branch as the first protein with the first protein and identifying at least one Variant amino acid Residue between the first protein and the second protein; (c) selecting at least one Candidate amino acid Residue from the Variant amino acid Residue identified in (b) on the basis of said Candidate amino acid Residue affecting said Target amino acid Residue with respect to said functional property; (d) forming at least one Candidate Mutant protein in silico or producing at least one Candidate Mutant protein in vitro in which said at least one Candidate amino acid Residue from the second protein substitutes a corresponding residue in the first protein; and (e) screeni

Abstract: The present invention relates to a method of differentiating mesenchymal stem cells or adult stem cells into nerve cells by treating the mesenchymal stem cells or the adult stem cells with an electromagnetic field having a high intensity of 100 to 1,500 mT and a low frequency of 0.01 to 100 Hz. The present invention also relates to a medical device to which the method is applied. The method of differentiating nerve cells by using a magnetic field, and a composition according to the present invention induce the differentiation of adult stem cells into nerve cells by using a low-frequency, high-intensity electromagnetic field, so that nerve cells or neural stem cells can easily be differentiated through only electromagnetic field treatment in a short time.

Abstract: The present invention relates to a sorbent material for separation and purification of biopolymers, particularly nucleic acids, having a solid support substantially modified with a copolymer coating comprising aromatic monomers and crosslinking compounds and unsaturated esters or ethers preferably attached to the support via a vinylchlorsilane. The use of these materials for separation of nucleic acids, particularly a one-step isolation of DNA from lysates of different biological sources, is an object of the invention as well as a chromatographic column or cartridge at least partially filled with the sorbent material of the invention, a membrane-like device comprising the sorbent material of the invention, and a kit comprising the sorbent material of the invention in bulk or packed in chromatographic devices as well as other devices necessary for performing sample preparations.

Abstract: The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

Abstract: The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

Abstract: The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

Abstract: The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

Abstract: Disclosed are methods, protocols, and compositions of matter useful for generation of lymphocytes with permanently inactivated immunological checkpoint genes, said genes comprising PD-1, CTLA-4, LAG-3, and TIM-3. The generated lymphocytes may be autologous or allogeneic, and are useful in the treatment of neoplastic, viral or bacterial infections.

Abstract: The present disclosure relates to compositions and methods for modifying a gene sequence, and for systems for deliverying such compositions. For example, the disclosure relates to modifying a gene sequence using a CRISPR-Cas9 or other nucleic acid editing system, and methods and delivery systems for achieving such gene modification, such as viral or non-viral delivery systems.

Abstract: Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems, using truncated guide RNAs (tru-gRNAs).

Abstract: A method for operating magnetic body particles that is for fixing a target substance in a liquid sample to the surface of the magnetic body particles; and a device for operating magnetic body particles that is used for said method. The magnetic body particles are particles to which a target substance can be fixed selectively. In this method, in a state where a liquid sample, the magnetic body particles, and a magnetic solid body that has a larger particle diameter than that of the magnetic body particle are made to coexist in a container, the magnetic body particles are moved together with the magnetic solid body within the liquid sample by operating a magnetic field from outside the container. By this operation, the target substance can be fixed selectively to the surface of the magnetic body particles.

Abstract: The present invention relates to a new method for enriching and/or isolating nucleic acids from microbial cells which comprises filtering a liquid sample through a nucleic acid-binding matrix which has a pore size small enough to retain microbial cells, lysing the microbial cells on the matrix to release the nucleic acids from the microbial cells, binding the nucleic acids to the matrix and subsequently eluting the DNA. The invention also relates to a method for enriching and/or isolating nucleic acids from microbial cells which are present in a liquid sample that comprises microbial cells and higher eukaryotic cells and/or tissues. The invention also provides a cartridge for carrying out the methods of the invention. Finally, the invention relates to kits for carrying out the methods of the invention.

Abstract: Aspects of the invention relate to methods for increasing gene expression in a targeted manner. In some embodiments, methods and compositions are provided that are useful for posttranscriptionally altering protein and/or RNA levels in a targeted manner. Aspects of the invention disclosed herein provide methods and compositions that are useful for protecting RNAs from degradation (e.g., exonuclease mediated degradation).

Abstract: The present invention relates to an oligonucleotide structure and a method for preparing the same and, more particularly, to an oligonucleotide structure in which a polymer compound is linked to an oligonucleotide via a covalent bond to improve in vivo stability of the oligonucleotide and cellular delivery efficiency of the oligonucleotide; and to a method for preparing the same.

Abstract: The invention relates to methods and uses of modulating fetal hemoglobin expression (HbF) in a hematopoietic progenitor cells via inhibitors of BCL11A expression or activity, such as RNAi and antibodies.

Abstract: The present application relates to a method for the targeted formation of heterochromatin and/or induction of epigenetic gene silencing in a cell using a small RNA, said method comprising the step of inhibiting the Paf1 complex in said cell and the step of contacting said cell with a small RNA targeted to a region of the genome of the cell, said region being the region where heterochromatin formation and/or induction of epigenetic gene silencing should be induced.

Abstract: The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Atonal homolog 1 (ATOH1), in particular, by targeting natural antisense polynucleotides of Atonal homolog 1 (ATOH1). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of ATOH1.

Abstract: What is described is a method for preparing a liposome that efficiently encapsulates a negatively charged therapeutic polymer, e.g., siRNA. The process involves preparing a lipid mixture comprising a cationic lipid in a water miscible organic solvent, such as ethanol, at a concentration of 2.3 mg/ml, and adding this solution to the polymer dissolved in water to a final concentration of 35% ethanol in water. The final charge ratio of drug:lipid is 1:2.5. The resulting nanoparticles have a mean size of 50 to 150 nm.

Abstract: The invention relates to a method for the treatment of amyotrophic lateral sclerosis (ALS). Specifically, the invention implements the use of an antisense sequence adapted to affect alternative splicing in a human SOD1 pre-mRNA, thereby leading to the destruction of the skipped m RNA by the cell machinery.

Abstract: The present invention relates to the field of gene therapy, more specifically to oligonucleotides for making a change in the sequence of a target RNA molecule present in a living cell

Abstract: Methods for making synthetic gene clusters are described.

Abstract: The present application provides novel regulatory elements including promoter sequences from microorganisms. The application further discloses DNA constructs containing these novel regulatory elements, and recombinant microorganisms comprising these regulatory elements. Methods of modifying, producing, and using the regulatory elements are also disclosed. The regulatory elements and transformation methods disclosed herein are particularly suited for use in Parachlorella and other microalgae.

Abstract: This disclosure provides purified nucleic acids and polypeptides. Also provided are transgenic plants, seeds, and plant cells containing DNA for expression of the proteins that are useful for imparting enhanced agronomic trait(s) to transgenic crop plants, methods of making such plants and methods of making agricultural commodity including seeds and hybrid seeds from such plants.

Abstract: The invention provides methods for engineering plants to have reduced levels of acetylation by decreasing expression of one or more Cas1L genes. Such plants can be used, e.g., to increase yield for biofuel production.

Abstract: The present invention relates to an improved method for the serum-free production of an immortalized human cell line stably transfected under serum-free conditions with a specific vector carrying the gene coding for the protein of interest. Furthermore the invention relates to a production cell line obtained by said method, a production method for said protein of interest utilizing said production cell line, and the specific vector carrying the gene of interest itself.

Abstract: The disclosure pertains to methods and compositions for treating disorders affecting the central nervous system (CNS). These disorders include neurometabolic disorders such as lysosomal storage diseases that affect the central nervous system, e.g., Niemann-Pick A disease. They also include disorders such as Alzheimer's disease. The disclosed methods involve contacting an axonal ending of a neuron with a composition containing high titer AAV carrying a therapeutic transgene so that the AAV vector is axonally transported in a retrograde fashion and transgene product is expressed distally to the administration site.

Abstract: The present invention relates nucleic acid constructs for the production of recombinant parvoviral (e.g. adeno-associated viral) vectors in insect cells, to insect cells comprising such constructs and to methods wherein the cells are used to produce recombinant parvoviral virions. The insect cells preferably comprise a first nucleotide sequence encoding the parvoviral rep proteins whereby the initiation codon for translation of the parvoviral Rep78 protein is a suboptimal initiation codon that effects partial exon skipping upon expression in insect cells. The insect cell further comprises a second nucleotide sequence comprising at least one parvoviral (AA V) inverted terminal repeat (ITR) nucleotide sequence and a third nucleotide sequence comprising a sequences coding for the parvoviral capsid proteins.

Abstract: Human or humanized tissues and organs suitable for transplant are disclosed herein. Gene editing of a host animal provides a niche for complementation of the missing genetic information by donor stem cells. Editing of a host genome to knock out or disrupt genes responsible for the growth and/or differentiation of a target organ and injecting that animal at an embryo stage with donor stem cells to complement the missing genetic information for the growth and development of the organ. The result is a chimeric animal in which the complemented tissue (human/humanized organ) matches the genotype and phenotype of the donor. Such organs may be made in a single generation and the stem cell may be taken or generated from the patient's own body. As disclosed herein, it is possible to do so by simultaneously editing multiple genes in a cell or embryo creating a “niche” for the complemented tissue.

Abstract: Disclosed herein are compositions for linking DNA binding domains and cleavage domains (or cleavage half-domains) to form non-naturally occurring nucleases. Also described are methods of making and using compositions comprising these linkers.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: Multi-carbon compounds such as ethanol, n-butanol, sec-butanol, isobutanol, tert-butanol, fatty (or aliphatic long chain) alcohols, fatty acid methyl esters, 2,3-butanediol and the like, are important industrial commodity chemicals with a variety of applications. The present invention provides metabolically engineered host microorganisms which metabolize methane (CH4) as their sole carbon source to produce multi-carbon compounds for use in fuels (e.g., bio-fuel, bio-diesel) and bio-based chemicals. Furthermore, use of the metabolically engineered host microorganisms of the invention (which utilize methane as the sole carbon source) mitigate current industry practices and methods of producing multi-carbon compounds from petroleum or petroleum-derived feedstocks, and ameliorate much of the ongoing depletion of arable food source “farmland” currently being diverted to grow bio-fuel feedstocks, and as such, improve the environmental footprint of future bio-fuel, bio-diesel and bio-based chemical compositions.

Abstract: The present invention provides methods for producing cannabinoids and cannabinoid analogs as well as a system for producing these compounds. The inventive method is directed to contacting a compound according to Formula I or Formula II with a cannabinoid synthase. Also described is a system for producing cannabinoids and cannabinoid analogs by contacting a THCA synthase with a cannabinoid precursor and modifying at least one property of the reaction mixture to influence the quantity formed of a first cannabinoid relative to the quantity formed of a second cannabinoid.

Abstract: This document describes biochemical pathways for producing 2,4-pentadienoyl-CoA by forming one or two terminal functional groups, comprised of carboxyl or hydroxyl group, in a C5 backbone substrate such as glutaryl-CoA, glutaryl-[acp] or glutarate methyl ester. 2,4-pentadienoyl-CoA can be enzymatically converted to 1,3-butadiene.

Abstract: Biomass (e.g., plant biomass, animal biomass, microbial, and municipal waste biomass) is processed to produce useful products, such as food products and amino acids.

Abstract: Disclosed herein are microorganisms containing exogenous or heterologous nucleic acid sequences, wherein the microorganisms are capable of growing on gaseous carbon dioxide, gaseous hydrogen, syngas, or combinations thereof. In some embodiments the microorganisms are chemotrophic bacteria that produce or secrete at least 10% of lipid by weight. Also disclosed are methods of fixing gaseous carbon into organic carbon molecules useful for industrial processes. Also disclosed are methods of manufacturing chemicals or producing precursors to chemicals useful in jet fuel, diesel fuel, and biodiesel fuel. Exemplary chemicals or precursors to chemicals useful in fuel production are alkanes, alkenes, alkynes, fatty acid alcohols, fatty acid aldehydes, desaturated hydrocarbons, unsaturated fatty acids, hydroxyl acids, or diacids with carbon chains between six and thirty carbon atoms long.

Abstract: A process for preparing a conjugated linoleic acid (CLA) material that is enriched in the cis 9, trans 11 (rumenic acid) CLA isomer. The process involves subjecting a material containing at least 75 weight % CLA moieties to an enzymatic conversion, wherein the enzyme has the ability to discriminate between the cis 9, trans 11 and trans 10, cis 12 isomers. The enzyme is advantageously a lipase derived from Candida rugosa. The resulting CLA product stream is distilled to separate the free fatty acid fraction from the glyceride fraction. The recovered free fatty acid fraction contains about 55 weight % to about 70 weight % of the cis 9, trans 11 isomer (rumenic acid), and has a weight ratio of cis 9, trans 11 isomer to trans 10, cis 12 isomer of at least 3.5:1. The material enriched in rumenic acid may be used in foods, particularly infant formulas, or in food supplements or in pharmaceutical compositions.

Abstract: The invention provides a recombinant microbial host cell capable of converting a raw material comprising a fermentable carbon substrate to o-aminobenzoate biologically. The invention further provides a method for producing aniline, comprising the steps of: a) producing o-aminobenzoate by fermentation of a raw material comprising at least one fermentable carbon substrate using the recombinant microbial host cell of the capable of converting said raw material comprising at least one fermentable carbon substrate to o-aminobenzoate biologically, wherein said o-aminobenzoate comprises anthranilate anion, b) converting said o-aminobenzoate from said anthranilate anion to anthranilic acid by acid protonation, c) recovering said anthranilic acid by precipitation or by dissolving in an organic solvent, and d) converting said anthranilic acid to aniline by thermal decarboxylation in an organic solvent.

Abstract: The disclosure relates to a method for transforming levoglucosenone into 4-hydroxymethyl butyrolactone or 4-hydroxymethyl butenolide, comprising a step involving the oxidation of the levoglucosenone, or dihydrolevoglucosenone obtained by hydrogenation of levoglucosenone, by bringing a solution of levoglucosenone or dihydrolevoglucosenone in a solvent into contact with a lipase in the presence of an oxidizing agent and an acyl donor compound. The oxidation step is followed by a step involving the hydrolysis of the reaction mixture obtained and, if necessary, a step involving the hydrogenation of the compound obtained at the end of the hydrolysis step.