Abstract: The invention relates to a highly stable polypeptide scaffold comprising an amino acid sequence based on a fibronectin type III (Fn3) domain and a polypeptide comprising the scaffold with grafted loops. The invention also relates to a nucleic acid molecule encoding the polypeptide scaffold, a method of making the polypeptide scaffold, and a composition comprising the polypeptide scaffold.

Abstract: The present disclosure provides a HTP microbial genomic engineering platform that is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols. This integrative platform utilizes a suite of HTP molecular tool sets to create HTP genetic design libraries, which are derived from, inter alia, scientific insight and iterative pattern recognition. The HTP genomic engineering platform described herein is microbial strain host agnostic and therefore can be implemented across taxa. Furthermore, the disclosed platform can be implemented to modulate or improve any microbial host parameter of interest.

Abstract: Provided herein are methods that enable parallel evaluation of multiple functional nucleic acids in individual cells or subpopulations of cells, in the context of incubation with other types of single cells. The key insight is concurrent measurement of polynucleic acids derived from small populations of at least two different cell types, such that function in one cell type is linked to the clonal identity of another cell. These methods simultaneously process thousands, millions, or more single cells or small populations of cells. The method integrates molecular, algorithmic, and engineering approaches. This invention has broad and useful application in a number of biological and medical fields, including immunology and drug discovery.

Abstract: The invention provides barcode libraries and methods of making and using them including obtaining a plurality of nucleic acid constructs in which each construct comprises a unique N-mer and a functional N-mer and segregating the constructs into a fluid compartments such that each compartment contains one or more copies of a unique construct. The invention further provides methods for digital PCR and for use of barcode libraries in digital PCR.

Abstract: In an illustrative embodiment, automated multi-module cell editing instruments are provided to automate multiple edits into nucleic acid sequences inside one or more cells.

Abstract: This disclosure relates to modified single and dual guide RNAs having improved in vitro and in vivo activity in gene editing methods.

Abstract: The present invention relates to, inter alia, pharmaceutical compositions comprising a polyunsaturated fatty acid and to methods of using the same to treat or prevent cardiovascular-related diseases.

Abstract: The present disclosure provides compositions comprising an antisense oligonucleotide and one or more excipients that modulates viscosity, turbidity or both viscosity and turbidity. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity are provided. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low turbidity are provided. In certain embodiments, pharmaceutical compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity and turbidity are provided.

Abstract: The invention features compositions and methods for treating and preventing pancreatic cancer.

Abstract: Provided herein are double-stranded nucleic acid inhibitor molecules having a sense strand with a stem loop structure and an antisense strand, where the stem portion of the stem loop structure contains one or more Tm-increasing nucleotides. Also provided are methods and compositions for reducing target gene expression and methods and compositions for treating a disease of interest.

Abstract: The invention relates to inhibitory nucleic acids and rAAV-based compositions, methods and kits useful for treating Amyotrophic Lateral Sclerosis.

Abstract: The invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the Serpina1 gene, and methods of using such RNAi agents to inhibit expression of Serpina1 and methods of treating subjects having a Serpina1 associated disease, such as a liver disorder.

Abstract: The invention is to methods of gene silencing in arthropods using dsRNA. The method is include contacting the arthropod with, and/or directly feeding the arthropod, the dsRNA to the arthropods to deliver the dsRNA to arthropod tissues. It is envisaged that the methods of the invention will have use in determining the biological function of genes in arthropods. Methods of pest control of arthropods, and of protecting arthropods against parasites and predators are provided. Transgenic arthropods expressing dsRNA molecules are also provided by the present invention.

Abstract: Compositions and methods for introducing double-stranded breaks within the SERPINA1 gene are provided. Compositions and methods for reducing and eliminating mutant forms of al-antitrypsin (AAT), such as seen in subjects having al-antitrypsin deficiency (AATD), are provided.

Abstract: Disclosed herein are polynucleotides, compositions, and methods for controlling insect pests, especially flea beetles, such as Phyllotreta spp. and Psylliodes spp., particularly in plants. More specifically, polynucleotides such as double-stranded RNA triggers and methods of use thereof for modifying the expression of genes in flea beetles.

Abstract: The present disclosure provides nucleic acid molecules, and kits comprising the same, for producing templated assembly products for a cell.

Abstract: The present disclosure relates to aptamers for temperature-dependent reversible inhibition of thermostable polymerase activity in order to improve sensitivity and specificity of various reactions and assays involving hot start polynucleotide synthesis. Methods for use of the aptamers and related compositions and kits are also provided.

Abstract: The invention relates to aptamers which specifically bind to fibrinogen and their use in the purification of said protein.

Abstract: The invention relates to a combination and its use for the treatment of diseases. The instant disclosure provides a combination of a so-called T-cell regulator selected from the group comprising PD1, PD-L1, OX40, TIM-3, LAGS, CD137(4-1BB) and a non-codiung immuno-modulating DNA.

Abstract: A therapeutic agent comprising a bacteria which expresses an inhibitor of MYC activity or a extract or product obtainable therefrom, for use in for use in the prevention or treatment o disease wherein MYC levels are elevated, such as cancer. Inhibitors of MYC activity comprising a factor obtainable from bacteria are novel and form a further aspect of the invention.

Abstract: Embodiments herein provide specially designed synthetic BCL11A-targeting microRNAs for RNA polymerase II expression, and methods of use to treat hemoglobinopathies such as sickle cell disease or thalassemia by increasing the expression levels of fetal hemoglobin levels.

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.

Abstract: The oligonucleotide compositions of the present invention make use of combinations of oligonucleotides. In one aspect, the invention features an oligonucleotide composition including at least 2 different oligonucleotides targeted to a target gene. This invention also provides methods of inhibiting protein synthesis in a cell and methods of identifying oligonucleotide compositions that inhibit synthesis of a protein in a cell.

Abstract: Efficient sequence specific gene silencing is possible through the use of siRNA technology. Be selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods compositions, and kits generated through rational design of siRNAs are disclosed, including those directed to the nucleotide sequences for F12.

Abstract: Disclosed are genetically engineered organisms, such as yeast and bacteria, that have the ability to metabolize atypical nitrogen sources, such as melamine and cyanamide. Fermentation methods using the genetically engineered organisms are also described. The methods of the invention are robust processes for the industrial bioproduction of a variety of compounds, including commodities, fine chemicals, and pharmaceuticals.

Abstract: Methods and compositions for gene disruption, gene editing or gene stacking within a FAD2 loci by cleaving, in a site directed manner, a location in a FAD2 gene in a soybean cell, to generate a break in the FAD2 gene and then optionally integrating into the break a nucleic acid molecule of interest is disclosed.

Abstract: The invention relates to gene expression regulatory sequences, specifically introns that act as enhancers of gene expression, the promoter and terminator sequences endogenously associated with these introns. Presence of these intronic enhancer sequences in proximity to promoter sequences leads to enhancement of gene expression. Methods of finding such new intronic enhancer sequences and using them to generate transgenic plants are also described.

Abstract: The present invention relates to a plant, which is resistant to a pathogen of viral, bacterial, fungal or oomycete origin, wherein the plant has a reduced level, reduced activity or complete absence of DMR6 protein as compared to a plant that is not resistant to the said pathogen, in particular organisms of the Fungi or the phylum Oomycota. The invention further relates to a method for obtaining a plant, which is resistant to a pathogen of viral, bacterial, fungal or oomycete origin, comprising reducing the endogenous level or activity of DMR6 protein in the plant. In addition, the invention relates to the use of a DMR6 promotor for providing disease resistant plants.

Abstract: The present invention includes systems, methods and compositions for the in vivo bioconversion of water-soluble cannabinoids in plant cell suspension cultures.

Abstract: Compositions and methods comprising polynucleotides and polypeptides that confer glufosinate resistance to a host cell are provided. Further provided are nucleic acid constructs, host cells, plants, plant cells, explants, seeds and grain having the sequence that confer glufosinate resistance. Various methods of employing these sequences are provided. Such methods include, for example, methods for producing a host cell, plant, plant cell, explant or seed having glufosinate resistance, and methods of controlling weeds in a field containing a crop employing the plants and/or seeds disclosed herein.

Abstract: The present invention relates to the field of plant breeding. More specifically, the present invention includes a method of using haploid plants for genetic mapping of traits of interest such as disease resistance. Further, the invention includes a method for breeding corn plants containing quantitative trait loci (QTL) that are associated with resistance to Gray Leaf Spot, a fungal disease associated with Cercospora spp.

Abstract: Compositions having pesticidal activity and methods for their use are provided. Compositions include isolated and recombinant polypeptides having pesticidal activity, recombinant and synthetic nucleic acid molecules encoding the polypeptides, DNA constructs and vectors comprising the nucleic acid molecules, host cells comprising the vectors, and antibodies to the polypeptides. Nucleotide sequences encoding the polypeptides can be used in DNA constructs or expression cassettes for transformation and expression in organisms of interest. The compositions and methods provided are useful for producing organisms with enhanced pest resistance or tolerance. Transgenic plants and seeds comprising a nucleotide sequence that encodes a pesticidal protein of the invention are also provided. Such plants are resistant to insects and other pests. Methods are provided for producing the various polypeptides disclosed herein, and for using those polypeptides for controlling or killing a pest.

Abstract: Compositions and methods for controlling plant pests are disclosed. In particular, novel insecticidal proteins having toxicity against Coleopteran and/or Lepidopteran insect pests are provided. Nucleic acid molecules encoding the novel insecticidal proteins are also provided. Methods of making the insecticidal proteins and methods of using the insecticidal proteins and nucleic acids encoding the insecticidal proteins of the invention, for example in transgenic plants to confer protection from insect damage, are also disclosed.

Abstract: Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitory factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.

Abstract: The present invention relates to a system for F-box hormone receptor regulated protein expression in mammalian cells. The system includes a silencing nucleic acid molecule comprising a first promoter and an shRNA operably linked to the first promoter, where the shRNA silences expression of a target protein. The system also includes an expression nucleic acid molecule comprising a second promoter, an F-box hormone receptor operably linked to the second promoter, and a nucleic acid molecule encoding a fusion protein comprising a degron fused to the target protein, where the nucleic acid molecule encoding the fusion protein is operably linked to the second promoter. Also disclosed are vectors comprising the system of the present application and methods of use thereof.

Abstract: Modified viral genomes are able to reduce induction of inflammatory and immune anti-viral responses. This manifests itself in reduced NF-kB activity, increased viral transduction rates, and increased expression of transgenes. Viral genomes are modified by incorporating one or more oligonucleotide sequences which are able to bind to TLR9 but not induce activation of it. The oligonucleotide sequences may be synthetic, bacterial, human, or from any other source.

Abstract: The invention provides an adenovirus or adenoviral vector characterized by comprising one or more particular nucleic acid sequences or one or more particular amino acid sequences, or portions thereof, pertaining to, for example, an adenoviral pIX protein, DNA polymerase protein, penton protein, hexon protein, and/or fiber protein.

Abstract: Methods and compositions are provided for delivery of a polynucleotide encoding a gene of interest, typically an antigen, to a dendritic cell (DC). The virus envelope comprises a DC-SIGN specific targeting molecule. The methods and related compositions can be used to treat patients suffering from a wide range of conditions, including infection, such as HIV/AIDS, and various types of cancers.

Abstract: A DNA construct containing an erythroid lineage-specific promoter operably linked to a nucleotide coding sequence of interest and a method of using the same in the prevention or treatment of a hematopoietic disorder such as a hemoglobinopathy are described. Further disclosed are erythroid-specific promoters and erythroid-specific enhancers that can be used in the DNA construct.

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: Complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide are provided. Compositions and methods for delivery of complexes comprising a nucleic acid-guided endonuclease, a sequence-specific targeting nucleic acid and an amphipathic helical peptide to mammals for both research and therapeutic use are provided. Methods of treating or reducing one or more symptoms of type 2 diabetes, prediabetes and/or gestational diabetes are provided.

Abstract: What is disclosed is a biorefining process to co-produce xylitol with ethanol or other products. In some variations, a process for producing ethanol and xylitol from lignocellulosic biomass, comprises: extracting hemicelluloses from lignocellulosic biomass, wherein the hemicelluloses include xylose oligomers and other sugar oligomers; hydrolyzing the xylose oligomers and the other sugar oligomers, using an acid catalyst or enzymes, to generate xylose and other sugar monomers, respectively; fermenting the other sugar monomers to ethanol using a suitable ethanol-producing microorganism; removing at least some of the ethanol (to increase concentration of xylose); fermenting the xylose to xylitol using a suitable xylitol-producing microorganism; and recovering the xylitol at high concentration.

Abstract: Genetically modified LeuCD? enzyme complexes, processes for preparing a C7-C11 2-ketoacid utilizing genetically modified LeuCD? enzyme complexes, and microbial organisms including modified LeuCD enzyme complexes are described. The instantly-disclosed genetically modified LeuCD? enzyme complexes, processes for preparing a C7-C11 2-ketoacid, and microbial organisms including modified LeuCD? enzyme complexes can be particularly useful for producing C6-C10 aldehydes, alkanes, alcohols, and carboxylic acids, both in vivo and in vitro.

Abstract: Improvement in C4 dicarboxylic acid productivity in a host cell is provided. A polypeptide consisting of the amino acid sequence represented by SEQ ID NO: 2 or an amino acid sequence having at least 90% identity therewith.

Abstract: In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, embodiments of the present disclosure, in some aspects, relate to genetically modified Streptomyces bacteria capable of increased thaxtomin production, genetically modified Streptomyces bacteria with reduced activity of a CebR protein encoded by a cebR gene and/or reduced activity of a ?-glucosidase enzyme encoded by the bglC gene, genetically modified Streptomyces bacteria including a mutation of a native cebR gene and/or a native bglC gene, methods of increasing thaxtomin production in Streptomyces bacteria, methods of suppressing CebR and/or BglC activity, methods of producing thaxtomin, and thaxtomin produced by the methods of the present disclosure.

Abstract: Methods are provided for reducing one or more dimensions of individual pieces of biomass; treating biomass, such as size-reduced biomass; changing a molecular structure of a biomass material; and, optionally, subjecting the biomass to a primary process to form a product. The methods include processing biomass materials using a screw extrusion process, and treating the biomass material with a screw extrusion process in size-reduction and treating steps.

Abstract: The present invention relates to processes for producing fermentation products from starch-containing material, wherein an alpha-amylase and a thermostable endoglucanase is present and/or added during liquefaction. The invention also relates to compositions suitable for use in processes of the invention.

Abstract: A method for enhancing extracellular vesicle production is described. A peptide that induces polymer formation is incubated with a cell culture which results in enhanced EV production. The peptide penetrates the cells and subsequently polymerizes upon exposure to enzymes (e.g. phosphatase) within the cell. The cells that contain the newly formed polymers have an increased production of EVs. These EVs can be harvested using centrifugation techniques.

Abstract: This invention is intended to identify a gene cluster involved in biosynthesis of a cyclic peptide compound produced by a filamentous fungus of the Curvularia species and to establish a system for synthesizing such cyclic peptide compound. The gene is composed of a first module to a tenth module and encodes a protein having activity of synthesizing a nonribosomal peptide constituting a basic peptide backbone of a cyclic peptide compound produced by a filamentous fungus of the Curvularia species.

Abstract: A method for the analysis of microorganisms, which produce a compound, the method comprising: a. providing a microorganism which produces a compound of interest and a detector microorganism which comprises a reporter gene or reporter gene operon, wherein the microorganism producing said compound of interest and the detector microorganism are combined into single droplets, wherein each droplet comprises at least one cell of each strain; b. subjecting the droplets to a microfluidic system; c. analyzing the droplets for the activation of the reporter gene of the detector strain; d. sorting and collecting the droplets comprising the detector microorganism with expressed reporter gene.