Abstract: Aspects of the disclosure relate to a gene therapy approach for diseases, disorders, or conditions caused by mutation in the stop codon utilizing modified tRNA. At least 10-15% of all genetic diseases, including muscular dystrophy (e.g. Duchene muscular dystrophy), some cancers, beta thalassemia, Hurler syndrome, and cystic fibrosis, fall into this category. Not to be bound by theory, it is believed that this approach is safer than CRISPR approaches due to minimal off-target effects and the lack of genome level changes.

Abstract: Methods and compositions are provided for modulating, e.g., reducing, coding sequence expression in mammals. In the subject methods, an effective amount of an RNAi agent, e.g., an interfering ribonucleic acid (such as an siRNA or shRNA) or a transcription template thereof, e.g., a DNA encoding an shRNA, is administered to a non-embryonic mammal, e.g., via a hydrodynamic administration protocol. Also provided are RNAi agent pharmaceutical preparations for use in the subject methods. The subject methods and compositions find use in a variety of different applications, including academic and therapeutic applications.

Abstract: Certain disclosed oligomers induce exon skipping during processing of myostatin pre-mRNA. The oligomers may be in a vector or encoded by the vector. The vector is used for inducing exon skipping during processing of myostatin pre-mRNA. A therapeutically effective amount of the oligomer may be administered to a subject patient such that exon skipping during processing of myostatin pre-mRNA is induced. The administration to a subject may be used in order to increase or maintain muscle mass, or slowing degeneration of muscle mass in the subject. The administration to a subject may ameliorate muscle wasting conditions, such as muscular dystrophy. Examples of such muscular dystrophies which may be so treated include Becker's muscular dystrophy, congenital muscular dystrophy, Duchenne muscular dystrophy, distal muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy (FSHD), limb-girdle muscular dystrophy, myotonic muscular dystrophy, and oculopharyngeal muscular dystrophy.

Abstract: The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the complement factor B (CFB) gene, the complement component C3 gene, and the complement component C9 gene and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of CFB, C9 and/or C3 and to treat subjects having a complement component-associated disease, e.g., paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

Abstract: The present invention relates to a technology for using a malate-aspartate shuttle (MAS) inhibitor as an agent for treating cancer. More particularly, provided is a pharmaceutical composition for preventing or treating cancer, containing, as an active ingredient, phenyl succinic acid, methyl malonic acid, N-(1-pyrenyl)maleimide and phthalonic acid, which are MAS inhibitors, or a mixture of the MAS inhibitor and an anticancer drug.

Abstract: The present disclosure provides for methods and compositions for treating cancer. A subject having lymphoma is administered an EZH2 inhibitor and an HDAC inhibitor. The combination of the EZH2 inhibitor and the HDAC inhibitor produces a synergistic effect on the cancer compared to the effect of the EZH2 inhibitor or the HDAC inhibitor alone.

Abstract: The present invention is directed to modified CRISPR-cas guides that modulate the activity of Cas9 polypeptides to which the synthetic guides are complexed. In addition, methods of use of the modified CRISPR-guides are provided.

Abstract: A method for the production of a functional prokaryotic membrane transporter protein in a eukaryotic host organism comprising the following steps: obtaining a DNA construct by ligating a DNA coding sequence of a prokaryotic membrane transporter protein to the N-terminal and/or C-terminal DNA coding sequences of a eukaryotic membrane protein; introducing the obtained DNA construct in the eukaryotic host organism for the production of the functional prokaryotic membrane transporter protein.

Abstract: The invention provides methods for genetically engineering Kluyveromyces. The methods can be used to genetically engineer Kluyveromyces to produce and secrete full-length antibodies or antibody fragments. The invention also provides methods for production and secretion of antibodies.

Abstract: Plant cell fate and development is altered by treating cells with cellular reprogramming factors. Embryogenesis inducing morphogenic developmental genes are used as cellular reprogramming factors, specifically comprising polypeptides or polynucleotides encoding gene products for generating doubled haploids or haploid plants from gametes. Maize microspores treated by contacting the isolated cells with an exogenous purified, recombinant embryogenesis inducing morphogenic developmental gene polypeptide results in embryogenesis. The gametes of a maize plant develop into embryoids when transformed with a genetic construct including regulatory elements and structural genes capable of acting in a cascading fashion to alter cellular fate of plant cells. Developmental morphogenic proteins expressed from a genetic construct are used for ex situ treatment methods and for in planta cellular reprogramming.

Abstract: The invention provides for systems, methods, and compositions for targeting nucleic acids. In particular, the invention provides non-naturally occurring or engineered DNA or RNA-targeting systems comprising a novel DNA or RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA.

Abstract: Provided is a recombinant vector including a new BiP gene fragment, and when a target protein is prepared using the recombinant vector of the subject matter, use stability can be enhanced and the production amount of target protein can also be increased by minimizing a foreign peptide sequence remaining in the target protein.

Abstract: The present invention provides methods and compositions for the identification and selection of loci modulating phenotypic expression of an herbicide tolerance trait in plant breeding. In addition, methods are provided for screening germplasm entries for the performance and expression of this trait.

Abstract: Compositions and methods comprising polynucleotides and polypeptides having EPSP (5-enolpyruvylshikimate-3-phosphate) synthase (EPSPS) activity are provided. In specific embodiments, the sequence has an improved property, such as, but not limited to, improved catalytic capacity in the presence of the inhibitor, glyphosate. Further provided are nucleic acid constructs, plants, plant cells, explants, seeds and grain having the EPSPS sequences. Various methods of employing the EPSPS sequences are provided. Such methods include methods for producing a glyphosate tolerant plant, plant cell, explant or seed and methods of controlling weeds in a field containing a crop employing the plants and/or seeds disclosed herein.

Abstract: A more efficient breeding against Cercospora leaf spot disease, or the development of new resistant lines, is enabled via the provision of the Cercospora resistance-mediating gene according to the invention; in particular, a dominant resistance effect in the target plant is evoked by the property of the identified gene alone. The Cercospora resistance-mediating gene, and embodiments of the present invention that are described in the preceding, offer additional applications, e.g., the use of the resistant gene allele in cis-genetic or trans-genetic approaches, with the goal of developing new resistant cultivars.

Abstract: The present invention relates to the field of self-replicating non-integrative episomal vertebrate expression vectors useful for in gene therapy, ex vivo cell therapy, stem cell therapy, and more particularly, for improving the expression of vector encoded antigens or therapeutic genes. Such recombinant DNA molecules are useful in biotechnology, transgenic organisms, gene therapy, stem cell therapy, therapeutic vaccination, agriculture and DNA vaccines. More specifically, relates to a polynucleotide comprising at least one promoter and an S/MAR element, wherein said S/MAR element is located downstream of said promoter and wherein the nucleic acid sequence of said S/MAR element (S/MAR sequence) comprises at least 3 sequence motifs ATTA (SEQ ID NO:1) per 100 nucleotides over a stretch of at most 200 nucleotides; the present invention further relates to a composition and to a host cell comprising said polynucleotide, and to the polynucleotide for use in medicine and for use in treating genetic disease.

Abstract: Described herein are cell compositions comprising an active cell (e.g., an engineered active cell, e.g., an engineered RPE cell) or derivatives thereof, as well as compositions, pharmaceutical products, and implantable elements comprising an active cell, and methods of making and using the same. The cells and compositions may express a therapeutic agent useful for the treatment of a disease, disorder, or condition described herein.

Abstract: The present disclosure provides a split intein selectable marker system for the production and selection of transgenic cells.

Abstract: Disclosed are methods and compositions for in situ germline genome engineering. The disclosed methods and compositions may be utilized for germline genome engineering in a subject having a reproductive organ containing a fertilized zygote, via: (i) isolating or obtaining the reproductive organ from the subject after a time period following insemination of the subject; (ii) introducing a reagent composition into the reproductive organ, the reagent composition comprising a nuclease system and/or an exogeneous polynucleotide; and (iii) electroporating the reproductive organ.

Abstract: Described herein are compositions and methods for treating Friedreich's Ataxia (FA) using adeno-associated virus (AAV) to deliver therapeutics agents.

Abstract: The present invention relates to a pharmaceutical composition for preventing or treating cardiac arrhythmia. Particularly, the present invention relates to a pharmaceutical composition containing, as an active ingredient, a CCN5 protein or a nucleotide encoding the same. The pharmaceutical composition for preventing or treating cardiac arrhythmia, of the present invention, inhibits the pathological activity of CaMKII, which induces cardiac electrical abnormalities which is the main cause of atrial arrhythmia and ventricular arrhythmia, so as to restore the electrical functions, and inhibits the activity of myofibroblasts causing structural abnormalities. Therefore, the pharmaceutical composition of the present invention can be effectively used in the prevention or treatment of cardiac arrhythmia.

Abstract: A recombinant vector comprises simian adenovirus 43, 45, 46, 47, 48, 49 or 50 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus 43, 45, 46, 47, 48, 49 or 50 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Abstract: Provided herein are methods for identifying high potency genomic insulator elements that can be used in a vector composition e.g., that are useful for preventing unwanted expression of neighboring genes, such as proto-oncogenes, when administered to a subject in need thereof. Also provided herein are methods for treating disease and methods for administering a nucleic acid to a subject using such vectors.

Abstract: The present invention provides robust, streamlined, reproducible and highly efficient eukaryotic cell transfection systems and related methods. The highly-efficient systems and methods of the present invention reduce the number of steps required to transfect cells and reduce, e.g., eliminate, the need for specialized equipment. In particular, the systems and related methods afford the ability for streamlining transfection while retaining and improving robust and reproducible transfection efficiencies, cell viability, and/or protein production. Furthermore, the highly-efficient systems and methods of the present invention for transfecting eukaryotic cells also eliminate the need for any specialized or complicated preparation of exogenous nucleic acid, which makes available high throughput and/or large scale transfection.

Abstract: The present invention relates to a CRISPR/Cas system having an inversion correction potential, which uses at least one guide RNA targeting a sequence region where two different homologs present on genomic introns are conjugated to each other in an inversion manner, and a Cas protein, and a CRISPR/Cas system of FVIII gene inversion correction potential that uses at least one guide RNA targeting an int22-1/3 homolog or int22-1/2 homolog sequence region present on intron 22 of coagulation factor VIII (F8) gene and a Cas protein. A CRISPR/Cas system according to the present invention comprises a system which employs a small-size Cas9 and a guide RNA fitted thereto, thereby enabling all CRISPR/Cas instruments to be easily packaged in one AAV, which is impossible in conventional large-size Cas9.

Abstract: The present invention provides high efficiency targeted and marker-less single or simultaneous multiple integrations using nucleases and a stable plasmid in Kluyveromyces host cells.

Abstract: Genome editing systems, guide RNAs, DNA donor templates, and CRISPR-mediated methods are provided for altering a ?-globin gene to alter a genotype, e.g., by correcting or partially correcting, a genotype associated with thalassemia or sickle cell disease.

Abstract: The present invention relates to a process for improving the nutritional quality of distillers dried grains (DGS) or distillers dried grains with solubles (DDGS) produced as a co-product of a fermentation product production process, processes for producing fermentation products, as well as enzyme blends used in the processes.

Abstract: A method of producing ethanol includes: a continuous ethanol fermentation step including culturing a microorganism with a fermentation feedstock containing cane molasses as a main component, filtering the resulting culture liquid through a separation membrane to recover a filtrate containing the ethanol and from which the microorganism has been removed; retaining or returning an unfiltered liquid containing the microorganism, in or to the culture liquid; and adding an additional fermentation feedstock to the culture liquid, and an ethanol concentration and purification step including distilling the filtrate collected in the continuous ethanol fermentation step and contains the ethanol, wherein the microorganism causes a centrifugal supernatant of the culture liquid to contain particles having an average particle diameter of 100 nm or more, and particles formed by the microorganism culture and contained in the filtrate containing ethanol have an average particle diameter of 40 to 80 nm.

Abstract: A process for producing a fuel from lignocellulosic biomass is disclosed. The process includes obtaining a feedstock comprising lignocellulosic biomass, feeding the feedstock and sulfur dioxide into a pretreatment reactor, wherein a total amount of sulfur dioxide in the pretreatment reactor is greater than 70 wt % based on dry weight lignocellulosic biomass, and heating the feedstock and sulfur dioxide in the pretreatment reactor at one or more temperatures between 110° C. and 150° C. for more than 60 minutes.

Abstract: The present invention provides biochemical pathways, glyoxylate producing recombinant microorganisms, and methods for the production and yield improvement of glycolic acid and/or glycine via a reverse glyoxylate shunt. The reverse glyoxylate shunt comprises an enzyme that catalyzes the carboxylation of phosphoenol pyruvate (PEP) to oxaloacetate (OAA), or an enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate (OAA) or an enzyme that catalyzes the carboxylation of pyruvate to malate or a combination of any of the previous reactions; an enzyme that catalyzes the conversion of malate to malyl-CoA; an enzyme that catalyzes the conversion of malyl-CoA to glyoxylate and acetyl-CoA; and optionally an enzyme that catalyzes the conversion of oxaloacetate (OAA) to malate. Glyoxylate is reduced to produce glycolate. Alternatively, glyoxylate is converted to glycine.

Abstract: The present disclosure pertains to a recombinant Corynebacterium glutamicum strain for production of glutaric acid and a method for production of glutaric acid by using the same. When used to produce glutaric acid, the recombinant Corynebacterium glutamicum strain guarantees an excellent output and allows the selective production of glutaric acid without generation of byproducts, which needs no isolation and purification processes and thus leads to an economical benefit. Consequently, the recombinant strain is useful for production of glutaric acid.

Abstract: Embodiments of the invention relate generally to processes for the production and processing of polyhydroxyalkanoates (PHA) from carbon sources. In several embodiments, PHAs are produced at high efficiencies from carbon-containing gases or materials.

Abstract: The present invention relates to methods for increasing the concentration of anthranilic acid tolerated by a given microbial cell by limiting the concentration of ammonia in the culture medium.

Abstract: The disclosure relates to host cells having altered NADPH availability, allowing for increased production of compounds produced using NADPH, and methods of use thereof. NADPH availability is altered by one or more of: expressing an altered GAPDH, expressing a variant glutamate dehydrogenase (gdh), aspartate semialdehyde dehydrogenase (asd), dihydropicolinate reductase (dapB), and meso-diaminopimelate dehydrogenase (ddh), expressing a novel nicotinamide nucleotide transhydrogenase, expressing a novel threonine aldolase, and expressing or modulating the expression of a pyruvate carboxylase in the host cells.

Abstract: Recombinant microorganisms configured for enhanced production of compounds such as 2-pyrone-4,6-dicarboxylic acid (PDC) and methods of using the recombinant microorganisms for the production of these compounds. The recombinant microorganisms include one or more modifications that reduce 2-pyrone-4,6-dicarboxylic acid (PDC) hydrolase activity, 4-carboxy-2-hydroxy-6-methoxy-6-oxohexa-2,4-dienoate (CHMOD) cis-trans isomerase activity, 4-carboxy-2-hydroxy-6-methoxy-6-oxohexa-2,4-dienoate (CHMOD) methyl esterase activity, and/or vanillate/3-O-methylgallate O-demethylase activity. The recombinant microorganisms can be used to generate PDC from media comprising plant-derived phenolics, such as syringyl phenolics, guaiacyl phenolics, and p-hydroxyphenyl phenolics. The plant-derived phenolics can be derived from pretreated lignin, including depolymerized lignin or other chemically altered lignin.

Abstract: The present invention relates to a newly isolated bacterium belonging to the genus Microbacterium, a composition for producing psicose comprising the strain, and a method for producing psicose using the same.

Abstract: The present disclosure relates to a composition for producing tagatose comprising a protein having fructose-4-epimerase activity and a method for producing tagatose using the same.

Abstract: The present disclosure relates to methods, processes and systems for enzymatic synthesis of oligonucleotide from a single-stranded, immobilized primer in the presence of a polymerase. Using the disclosed methods single-stranded oligonucleotides can be synthesized enzymatically from a single-stranded, immobilized primer in the presence of deoxyribonucleotide triphosphates or ribonucleotide triphosphates. Dideoxyribonucleotide triphosphates, deoxyribonucleotide triphosphates with reversible terminators, or ribonucleotide triphosphates with reversible terminators can be added enzymatically to the end of the primer or its extension products. According to the disclosed method, a single-stranded primer can bind to a template such that the thus-formed double-stranded structure can allow the polymerase to extend the primer at 3? end.

Abstract: A method for producing an objective protein and a method for producing a disaccharide are provided. An objective protein is produced by culturing Talaromyces cellulolyticus in a culture medium containing an expression inducer such as gentiobiose. A disaccharide is produced from a saccharide raw material by enzymatic conversion using a disaccharide synthesizing enzyme.

Abstract: The present invention relates to a method for increasing the O-glycan heterogeneity of recombinant Factor VII (FVII). In particular, the present invention relates to a method for reducing the occurrence of Xyl-Xyl-Glc-glycosylation of FVII. The present invention further relates to uses, compositions of matter, recombinant FVII prepared by the method of the invention, pharmaceutical compositions comprising recombinant FVII prepared by the method of the invention and medical uses of recombinant FVII prepared by the method of the invention.

Abstract: Methods and compositions for making bacteriocins are described in some embodiments herein. In some embodiments, pro-polypeptide comprising the bacteriocins in the desired ratios in cis, and separated by cleavage sited can be produced by a microbial cell comprising a nucleic acid encoding the pro-polypeptide. In some embodiments microfluidic devices and methods for making specified mixtures of antimicrobial peptides and/or bacteriocins are described.

Abstract: A method for producing imidazole dipeptide using a microorganism having imidazole dipeptide synthesis activity, the production method not including adding ATP, or including adding an amount of ATP that is less than the amount of imidazole dipeptide that is produced in terms of the number of moles, by utilizing an ATP supply system of the microorganism.

Abstract: Methods for assessing microbiota are disclosed. An example method for assessing microbiota may include obtaining a fecal sample from a patient, quantifying the relative abundance of bacteria from a selected group of taxonomic classes in the fecal sample, calculating a microbiome health index based on the relative abundance of bacteria from the selected group of taxonomic classes, and correlating the microbiome health index with a medical condition of the patient.

Abstract: A method for determining the susceptibility of bacteria in a clinical sample comprising urine or an inoculant derived therefrom to an antibiotic agent may include the steps of a) inoculating a test portion of the clinical sample in a medium containing a predetermined concentration of the antibiotic agent; b) inoculating a control portion of the clinical sample in a medium that does not contain the antibiotic agent; c) incubating the test portion for an incubation period; d) incubating the control portion for the incubation period; e) determining a quantity of RNA in the test portion and a quantity of RNA in the control portion at the conclusion of the incubation period that is less than 480 minutes after the completion of step a); and f) determining a susceptibility of the bacteria to the antibiotic agent by comparing the quantity of RNA in the test portion to the quantity of the RNA in the control portion.

Abstract: The invention relates to a method for the identification of a first microorganism potentially secreting an effector compound, said first microorganism thereby having either i. an inhibitory effect on the cell division activity of a second microorganism or ii. an enhancing effect on the cell division activity of a second microorganism, the method comprising: a. providing a cell from a first microorganism which potentially produces an effector compound of interest and a cell from a second detector microorganism; b. introducing both cells into a microdroplet for incubation; c. introducing the microdroplet into a microfluidic system; d. analyzing in said microfluidic system the cell of the second microorganism for the exhibition of an enhanced growth effect or the exhibition of an inhibited growth effect stemming from said effector compound. The invention also relates to a microorganism or effector compound identified by the method according to the invention.

Abstract: A method for rapidly determining effective sterilization, deimmunization, and/or disinfection of equipment and/or supplies by a device. The method includes providing a defined surrogate protein having a predetermined sequence representative of an infectious agent potentially contaminating the equipment and/or the supplies to be sterilized, deimmunized, and/or disinfected by the device. The defined surrogate protein having the predetermined sequence is subjected to sterilization, deimmunization, or disinfection. The effectiveness of the sterilization deimmunization, or disinfection is rapidly determined by determining if the defined surrogate protein has been destroyed.

Abstract: A method of transferring material from a first microfabricated device to a second microfabricated device. At least one magnetic bead is loaded into at least one microwell of the first microfabricated device, where a plurality of cells are cultivated. The second microfabricated device is positioned such that the at least one microwell of the first array of microwells is aligned with at least one microwell of the second array of microwells. A magnetic field is applied so as to move the at least one magnetic bead contained in the at least one microwell of the first microfabricated device into the at least one microwell of the second microfabricated device. In this manner, at least one cell from the plurality of cells in the at least one microwell of the first microfabricated device is transferred to the at least one microwell of the second microfabricated device.

Abstract: Provided is a composition by which glycated hemoglobin can be measured even in the presence of a stronger surfactant than a conventional case. Also provided is a buffer and/or stabilizer which maintains the residual activity of an amadoriase or lowers a reduction of residual activity. The present invention provides a composition for use in measuring glycated hemoglobin containing an amadoriase having substitution of one or more amino acid residues at a position(s) corresponding to an amino acid(s) selected from the group consisting of position 262, position 257, position 249, position 253, position 337, position 340, position 232, position 129, position 132, position 133, position 44, position 256, position 231 and position 81 of an amadoriase derived from the genus Coniochaeta and represented by SEQ ID No: 1 or 3, and having residual activity even in the presence of a surfactant.

Abstract: Described are substituted imidazo[1,2-a]pyrazine compounds, which are coelenterazine analogues, kits comprising the analogues, and methods of using the compounds for the detection of luminescence in luciferase-based assays. Also described are methods from making the compounds, such as a method using aminopyrazine acetophosphonates as synthesis intermediates.