Abstract: Polypeptides for use in suppressing cancer and cancer disorders and methods of treatment using such polypeptides.

Abstract: The present disclosure relates to proteases comprising an amino acid sequence which has at least about 70% sequence identity to the amino acid sequence indicated in SEQ ID NO. 1, over the entire length thereof, and in which the amino acids in the positions corresponding to positions 24, 33, 53, 78, 101, 128 and 217 according to SEQ ID NO. 1 are substituted at 24G, 33T, 53G, 78N, 101N, 128A and 217Q, and to the production and use thereof. Said type of proteases have a very good cleaning performance compared to reference proteases.

Abstract: Disclosed are methods and isolated cells useful for the improved production of function fXa derivative protein that acts as a fXa inhibitor antidote. One aspect relates to an isolated cell comprising the r-Antidote polynucleotide and Furin polynucleotide. Another aspect relates to a method for preparing the cleaved two-chain r-Antidote by expressing, in a cell, the pre-processed r-Antidote polypeptide and a Furin polypeptide.

Abstract: Provided herein are modified caspase-9 polypeptides, and chimeric caspase-9 proteins containing the modified caspase-9 polypeptides. The disclosure further provides polynucleotides encoding these proteins, engineered host cells containing these polynucleotides and proteins, including host cells that co-express a chimeric antigen receptor, and methods of making and using the same.

Abstract: Alginate lyase activity is exhibited by the amino acid sequences (polypeptides) shown in SEQ ID No:1 and SEQ ID No:2. These polypeptides and their homology equivalents are used to produce 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEH) by contacting the polypeptide(s) with an alginate containing a uronic acid moiety and holding the mixture of the alginate and the polypeptide(s) at a temperature at which alginate lyase activity is exhibited.

Abstract: Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering metabolism in a cell using isolated and/or purified polypeptides and nucleic acid sequences from Alicyclobacillus acidocaldarius.

Abstract: The present invention provides compositions and methods relating to protein replacement therapy for the treatment of disorders associated with Methylmalonyl CoA Mutase.

Abstract: The present invention provides various combinations of genetic modifications to a transformed host cell that provide increase conversion of carbon to a chemical product. The present invention also provides methods of fermentation and methods of making various chemical products.

Abstract: Compositions and methods for delivering enzymes in enzyme hydrogel formulations are disclosed. More particularly, the present disclosure relates to injectable enzyme hydrogel formulations and delivery of injectable enzyme hydrogel formulations. Also disclosed are methods for GALNS enzyme replacement therapy and lysosomal enzyme replacement therapy.

Abstract: The present invention provides a method for extracting polyhydroxyalkanoates (PHAs), which comprises a pre-process step and an extraction step: removing water from waste sludge containing microorganisms in the pre-process step so that the waste sludge containing microorganisms has a water content of less than 40%; and applying a high-voltage pulsed electric field to the waste sludge during the extraction step to destroy the microorganisms and release the PHAs, wherein the high-voltage pulsed electric field is between 50 volts and 400 volts, an application time of the high-voltage pulsed electric field is between 5 seconds and 90 seconds, and an application frequency of the high-voltage pulsed electric field is between 500 Hz and 1000 Hz, thereby extracting the PHAs in the case of few chemicals.

Abstract: Provided herein are methods and systems for cell-free DNA extraction from liquid biological samples. The methods can be employed for determination of fetal DNA fraction and non-invasive prenatal screening of fetal aneuploidies and analyses of other types of cell-free DNA.

Abstract: The invention relates to a composition for stabilizing the total nucleic acids from whole blood, in particular RNA, and to a process for stabilizing the total nucleic acids from whole blood for subsequent isolation and at the same time serves for the disruption of cells so that cellular nucleic acids in the state at contacting the composition, especially at the point of time of blood collection, are released and are maintained stable in respect of quality and concentration and can be isolated subsequently. Therein, the composition is characterized in that it especially prevents the degradation and new synthesis of RNA in whole blood, into which it is mixed. The isolation of RNA by contacting the mixture of the aqueous composition and blood with an adsorption agent can be made directly from the complete mixture of the aqueous composition with blood, i.e. e.g. without precipitation and separation of nucleic acids from the mixture, optionally after a storage, during which the mixture is e.g.

Abstract: A binding agent to a target molecule, or method or kit where the binding agent is selected from a library where each variant has a circular permutation of the FHA domain where the rearrange does not substantially disrupt the FHA domain's beta-sheet scaffold or increase the stability of the beta-sheet scaffold. The randomized regions of the FHA domain include the endogenous binding interface the FHA domain, the region opposite of the endogenous binding interface, and the circular permutation region.

Abstract: Provided herein are methods for preparing nucleic acid molecules for sequencing. The methods may include generation of individual partitions (e.g., droplets or wells) including a biological particle and a bead comprising a nucleic acid barcode molecule. The preparation of barcoded nucleic acid molecules for sequencing can include subjecting the nucleic acid molecule to DNase treatment followed by attachment of a nucleic acid barcode molecule.

Abstract: Methods for the identification of agents the bind to exo-sites of proteins are provided. Agents identified by the methods described herein and pharmaceutical compositions comprising the identified agents are also provided. Methods of using an identified agent for the treatment or prevention of a disease, disorder, or condition are also provided, including methods of treating or preventing a disease associated with reduced, elevated, or ectopic expression or aberrant activity of a protein comprising an exo-site.

Abstract: Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

Abstract: The present invention relates to synthetic oligonucleotide mimetics of miRNAs. In particular, the present invention provides double-stranded, chemically-modified oligonucleotide mimetics of miR-29. Pharmaceutical compositions comprising the mimetics and their use in treating or preventing conditions associated with dysregulation of extracellular matrix genes, such as tissue fibrotic conditions, are also described.

Abstract: Provided are LMNA-targeted antisense oligonucleotides for reducing expression of one or more aberrantly spliced LMNA mRNA isoforms that encode progerin.

Abstract: Increase of energy expenditure as an effective treatment of obesity and related disorders is a target for drug research and development. A 15% increase of energy expenditure is believed to be sufficient to achieve significant weight and fat mass reduction while providing meaningful improvement of metabolic parameters. Disclosed herein is a method for pharmacological inhibition of miR-22-3p, which represents a new therapeutic approach for treating human obesity, diabetes, and hypercholesterolemia.

Abstract: The present disclosure pertains generally to chemically-modified oligonucleotides for use in research, diagnostics, and/or therapeutics. In certain embodiments, the present disclosure describes compounds and methods for the modulation of a target nucleic acid. In certain embodiments, the present disclosure describes compounds and methods for the modulation of Apoliprotein C-III expression.

Abstract: Provided are antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping, and methods of use thereof to treat muscular dystrophy.

Abstract: Disclosed herein are three-dimensional cage molecules, wherein the cage molecule is composed of RNA. Also disclosed is a composition including the three-dimensional cage molecule, as well as a pharmaceutical composition containing the three-dimensional cage molecule. Also disclosed herein are methods of administering a cage molecule, composition, or formulation thereof to a subject in need thereof.

Abstract: The present invention relates to methods and compositions for treating and/or preventing allergic diseases or conditions by inhibiting one or more components of the steroidogenic pathway.

Abstract: The invention provides compositions and methods for regulating intracellular osmolarity in cells, e.g., in cultured cells, including in cultured cells in bioreactors. The invention provides nucleic acids comprising at least one osmo-responsive transcriptional regulatory element (OR-TRE), and cells, vectors, products of manufacture, artificial organs or implants and the like containing an osmo-responsive transcriptional regulatory element (OR-TRE).

Abstract: Provided herein are methods of production of recombinant Erwinia asparaginase. Methods herein produce asparaginase having high expression levels in the periplasm or the cytoplasm of the host cell having activity comparable to commercially available asparaginase preparations.

Abstract: Provided herein are methods of production of recombinant E. coli asparaginase. Methods herein allow production of asparaginase in Pseudomonadales host cells at high expression levels and having activity comparable to commercially available asparaginase preparations.

Abstract: Provided herein are bacterial leader sequences for periplasmic expression of heterologous proteins, fusion proteins comprising bacterial leader sequences, and methods of expression of same.

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: Provided are isolated polynucleotides and nucleic acid constructs which comprise a nucleic acid sequence at least 80% identical to a nucleic acid sequence selected form the group consisting of SEQ ID NOs: 1-219, 367-5628, 9688-9700, and 9709-9752; and isolated polypeptides which comprise an amino acid sequence at least 80% homologous to an amino acid sequence selected from the group consisting of SEQ ID NOs: 220-366, 5629-9400, 9701-9708, and 9753-9796. Also provided are transgenic cells and plants expressing same and methods of using same for increasing yield, growth rate, biomass, vigor, oil content, seed yield, fiber yield, fiber quality, nitrogen use efficiency, and/or abiotic stress of a plant.

Abstract: The present invention relates to Brassica sequences comprising early stage seed-specific and endosperm preferential promoter activity. Provided are recombinant genes comprising the early stage seed-specific and endosperm preferential promoter operably linked to a heterologous nucleic acid sequence, and cells, plants and seeds comprising the recombinant gene. The promoters can be used to alter gene expression specifically in the seeds at early developmental stages and preferentially in the endosperm and to alter biotic or abiotic stress tolerance, yield, seed quality or seed properties.

Abstract: The present invention relates to Brassica sequences comprising seed- and funiculus-preferential promoter activity. Provided are recombinant genes comprising the seed- and funiculus-preferential promoter operably linked to a heterologous nucleic acid sequence, and cells, plants and seeds comprising the recombinant gene. The promoters can be used to alter gene expression preferentially in the seeds and in the funiculus and to alter biotic or abiotic stress tolerance, yield, seed quality or seed properties.

Abstract: Polynucleotides and polypeptides incorporated into expression vectors are introduced into plants and were ectopically expressed. These polypeptides may confer at least one regulatory activity and increased yield, increased resource use efficiency, increased water use efficiency, increased light use efficiency, increased photosynthetic capacity, increased photosynthetic rate, increased photosynthetic resource use efficiency, greater vigor, and/or greater biomass as compared to a control plant.

Abstract: The present invention provides means for inhibiting the bolting and flowering of a Beta vulgaris plant, including an isolated nucleic acid, which can be used to produce a transgenic Beta vulgaris plant, where bolting and flowering is inhibited after vernalization. Furthermore, the invention discloses vectors, transgenic and non-transgenic, non-bolting plants and parts thereof, and methods for producing such plants.

Abstract: Provided are isolated polynucleotides comprising a nucleic acid sequence encoding a polypeptide at least 80% identical to SEQ ID NO: 422, 362-421, 423-601, 2429-4085 and 4086, such as a polynucleotide which is at least 80% identical to SEQ ID NO: 260, 1-259, 261-361, 602-2427 and 2428, nucleic acid constructs comprising same, plant cells comprising same, transgenic plants expressing same, and methods of generating thereof for increasing the yield, biomass, growth rate, vigor, oil content, fiber yield, fiber quality, nitrogen use efficiency and/or abiotic stress tolerance of a plant.

Abstract: Polynucleotides and isolated polypeptides, nucleic acid constructs comprising the isolated polynucleotides, transgenic plants expressing same and methods of using same for increasing abiotic stress tolerance, yield, biomass, growth rate, vigor, oil content, fiber yield, fiber quality, and/or nitrogen use efficiency of a plant are disclosed.

Abstract: The present invention relates to a method for modifying the resistance profile of a spinach plant to Peronospora farinosa f. sp. spinaciae, comprising introducing a WOLF allele or a resistance-conferring part thereof into the genome of said spinach plant, or modifying an endogenous WOLF allele in the genome of said spinach plant. A WOLF allele encodes a CC-NBS-LRR protein that comprises in its amino acid sequence: the motif “MAEIGYSVC” at its N-terminus, and the motif “KWMCLR” for alpha-type WOLF proteins or “HVGCVVDR” for beta-type WOLF proteins. The invention relates to the WOLF alleles referred to in Table 3. The invention further provides a method for selecting a spinach plant comprising a novel WOLF gene that confers resistance to Peronospora farinosa f. sp. spinaciae in a spinach plant and a method for identifying a WOLF allele that confers resistance to one or more pathogenic races of Peronospora farinosa f. sp. spinaciae in a spinach plant and to primers for use in these methods.

Abstract: This disclosure concerns nucleic acid molecules and methods of use thereof for control of pathogens through RNA interference-mediated inhibition of target coding and transcribed non-coding sequences in pathogens. The disclosure also concerns methods for applying dsRNA through formulations and/or transgenic plants that express nucleic acid molecules useful for the control of pathogens, and the plant cells and plants obtained thereby.

Abstract: Genetic constructs are provided at least a fragment of which are insertable into the genetic material of a plant, wherein at least a fragment of the genetic construct comprises, consists essentially of, or consists of one or more nucleotide sequences derived from one or more plants. Also provided is use of the genetic construct for the production of genetically improved plants, and improved plants improved thereby. The improved plants may have desirable disease resistance, abiotic stress tolerance, or nutritional, palatability, or morphological properties.

Abstract: The present invention concerns concatemer and/or stabilized RNA constructs capable of forming dsRNA, optionally comprising a sequence capable of protecting the dsRNA against RNA processing in a host cell. The invention also relates to methods of producing these constructs and to methods for using these constructs. The constructs according to the present invention are particularly useful in plant pest control.

Abstract: The invention relates to a long DH (LDH) cassette comprising a recombinant DH construct comprising at least two DH gene segments encoding at least 10 amino acids of the HCDR3 amino acid sequence, wherein at least one of the DH gene segments is a heterologous DH gene segment; an immunoglobulin heavy chain locus and a transgenic non-human animal comprising the same; and their use in producing an immunoglobulin library with long HCDR3 regions.

Abstract: The present invention relates to methods and compositions for the production of viral vectors. In particular, the present invention provides methods and compositions for faster, higher titer and higher purity production of viral vectors (e.g. adenoviral vectors). In some embodiments, the present invention provides gutted and helper viruses with identical or similar termini. In other embodiments, the present invention provides terminal protein linked adenoviral DNA. In certain embodiments, the present invention provides template extended adenoviral DNA.

Abstract: The present invention provides novel multigenome retroviral vectors, methods and packaging systems for making such retroviral vectors and methods of use.

Abstract: The present invention provides improved methods for gene delivery to, or genetic modification of target cells, wherein the gene delivery or other genetic modification of the target cells is performed in the presence of endothelial cells, or after co-culture of the target cells with endothelial cells, or wherein co-culture of the target cells with endothelial cells is employed immediately alter gene delivery in order to “rescue” cells that may have been damaged during the gene delivery process. In some embodiments gene delivery is performed by transfection. In some embodiments gene delivery is performed by transduction, in some embodiments the endothelial cells are organ-specific endothelial cells. In some embodiments the endothelial cells are E40RF1-expressing endothelial cells (E40RF1+ ECs). In some embodiments the target cells are stem cells, such as hematopoietic stem cells.

Abstract: Systems and methods for transfection devices are contemplated for delivery of various complex macrostructures. Preferred systems and methods are suitable for mRNA reprogramming and genome editing and use mechanical force to induce uptake of the macrostructures in a target cell. Contemplated devices are able to achieve high throughput of transfected cells in remarkably short time that remain viable and are capable of producing colonies.

Abstract: Inhibiting p53 or Bax can be used to improve nuclease-mediated gene targeting frequencies in stem cells. This inhibition can be achieved, e.g., by overexpression of anti-apoptosis proteins or by silencing or reducing p53 or Bax expression. This technique can be used in conjunction with other rapidly developing CRISPR technologies, including improvements in specificity, other types of nucleases, and further enrichment, screening, and selection schemes, to expand the use of stem cells in experimental studies and tissue engineering for therapeutic purposes.

Abstract: A method for microbial fermentation of botanicals includes steps of: fermenting with wall-breaking fungi, and then fermenting with probiotics.

Abstract: The invention provides non-naturally occurring microbial organisms having a butadiene or crotyl alcohol pathway. The invention additionally provides methods of using such organisms to produce butadiene or crotyl alcohol.

Abstract: A recombinant yeast cell, fermentation compositions, and methods of use thereof are provided. The recombinant yeast cell includes at least one heterologous nucleic acid encoding one or more polypeptide having phosphoketolase activity; phosphotransacetylase activity; and/or acetylating acetaldehyde dehydrogenase activity, wherein the cell does not include a heterologous modified xylose reductase gene, and wherein the cell is capable of increased biochemical end product production in a fermentation process when compared to a parent yeast cell.

Abstract: The present invention provides a method for producing lactic acid in a recombinant yeast cell culture using glucose as carbon source comprising a first, seed fermentation stage to produce biomass wherein the yeast is cultivated in a culture medium at a pH of 5 to 7, followed by a second, a production fermentation stage with biomass from the seed fermentation to produce lactic acid, wherein the yeast is cultivated in a culture medium at low p H using a yeast strain that is engineered to have lactate dehydrogenase (LDH) activity and optionally has decreased or knocked-out pyruvate decarboxylase (PDC) activity.

Abstract: A method for producing an octaketide derived aromatic compound of interest (e.g. carminic acid), wherein the method comprises (I): heterologous expression of a recombinantly introduced Type III polyketide synthase (PKS) gene encoding an octaketide synthase (OKS) to obtain non-reduced octaketide in vivo within the recombinant host cell and (II): converting in vivo the non-reduced octaketide of step (I) into a C14-C34 aromatic compound of interest (e.g. carminic acid).