Abstract: An in vitro microfluidic intestine on-chip is described herein that mimics the structure and at least one function of specific areas of the gastrointestinal system in vivo. In particular, a multicellular, layered, microfluidic intestinal cell culture, which is some embodiments is derived from patient's enteroids-derived cells, is described comprising L cells, allowing for interactions between L cells and gastrointestinal epithelial cells, endothelial cells and immune cells. This in vitro microfluidic system can be used for modeling inflammatory gastrointestinal autoimmune tissue, e.g., diabetes, obesity, intestinal insufficiency and other inflammatory gastrointestinal disorders. These multicellular-layered microfluidic intestine on-chips further allow for comparisons between types of gastrointestinal tissues, e.g., small intestinal duodenum, small intestinal jejunum, small intestinal ileum, large intestinal colon, etc., and between disease states of gastrointestinal tissue, i.e.

Abstract: The present disclosure relates to a world first and only authentic EBV-positive cisplatin-resistant NPC PDX, xeno76-CR, which has been tested with different examinations and is confirmed as cisplatin-resistant EBV-positive undifferentiated human NPC. Xeno76-CR is a valuable preclinical model that mimics the NPC patients who have failed chemotherapy. It could predict the treatment outcome in drug testings, increase the success rate for new therapeutic agents when proceed into clinical trial, and ultimately benefit NPC patients with more choices of promising therapy.

Abstract: Devices, systems, and techniques are described for printing pre-aligned microtissues into larger tissue constructs. For example, a method of printing a tissue construct includes aligning cells in a first direction to create pre-aligned microtissues, suspending the pre-aligned microtissues in a liquid to create a bioink, and depositing the pre-aligned microtissues in a second direction to create the tissue construct.

Abstract: The present disclosure relates to an organ bud and a method of preparing an organ bud.

Abstract: The present disclosure provides, among other things, Ad35 helper genomes and vectors useful in gene therapy, e.g., for production of helper-dependent Ad35 donor vectors. Helper genomes of the present disclosure include a conditionally defective packaging sequence.

Abstract: Methods for continuously inactivating a virus during manufacture of a protein are provided. Steps include (1) combining, at a single predetermined volumetric ratio, a composition including the protein, and a composition including a virus-inactivation reagent, to obtain a treatment composition having a predetermined property for inactivation of a virus; (2) transferring the treatment composition to a treatment vessel; (3) incubating the treatment composition in the treatment vessel at predetermined conditions; and (4) subjecting the treatment composition to a post-treatment processing operation. The single predetermined volumetric ratio has been selected to ensure that the predetermined property of the treatment composition is maintained across a range of concentrations predicted for the protein in the composition including the protein.

Abstract: The present invention provides compositions of CD180 targeting molecules coupled to heterologous antigens, and their use in treating and/or limiting disease.

Abstract: The present invention relates to an oncolytic virus which is, or is derived from, a clinical isolate which has been selected by comparing the abilities of a panel of three or more clinical isolates of the same viral species to kill tumor cells of two or more tumor cell lines in vitro and selecting a clinical isolate which is capable of killing cells of two or more tumor cell lines more rapidly and/or at a lower dose in vitro than one or more of the other clinical isolates in the panel.

Abstract: The disclosure relates to engineered ketoreductase polypeptides and processes of using the polypeptides for production of phenylephrine.

Abstract: The present invention provides engineered peroxidase enzymes, polypeptides having peroxidase activity, and polynucleotides encoding these enzymes, as well as vectors and host cells comprising these polynucleotides and polypeptides. Methods for producing peroxidase enzymes are also provided. The present invention further provides compositions comprising the peroxidase enzymes and methods of using the engineered peroxidase enzymes. The present invention finds particular use in the production of pharmaceutical and other compounds.

Abstract: Recombinant peroxidase enzymes are disclosed having mutations that increase yield when expressed in yeast cells as compared to their corresponding wild-type peroxidase enzyme. Methods of generating are also disclosed as well as uses thereof.

Abstract: The present disclosure relates to the field of bioengineering and pharmaceutical and chemical production. In particular, provided is a polynucleotide comprising a coding sequence of toluene dioxygenase. Also provided are an expression cassette, a vector and a host cell comprising the polynucleotide, as well as use thereof in the preparation of cis-cyclohexadiene o-diol compounds.

Abstract: The present invention is directed to ligand binding molecules and uses thereof to modulate angiogenesis and/or lymphangiogenesis.

Abstract: The present disclosure relates to systems, compositions and methods for modifying target nucleic acid sequences.

Abstract: Embodiments of the present disclosure are directed to methods and compositions for reducing or eliminating latent HSV-1 reactivation in a cell. In some embodiments, the method comprises delivering to an HSV-1-infected cell one or more self-complementary adeno-associated viruses (scAAV) comprising one or more sequences encoding one or more HSV-1-specific meganucleases. In some embodiments, the composition comprises one or more self-complementary adeno-associated viruses (scAAV) comprising one or more sequences encoding one or more HSV-1-specific meganucleases.

Abstract: The invention relates to compositions and methods for targeting polynucleotides with eukaryotic RNA-guided nucleases. In particular, programmable RNA-guided DNA endonucleases termed Fanzors, can be harnessed for genome editing.

Abstract: The present disclosure provides systems and methods for transposing a cargo nucleotide sequence to a target nucleic acid site. These systems and methods may comprise a first double-stranded nucleic acid comprising the cargo nucleotide sequence, wherein the cargo nucleotide sequence is configured to interact with a recombinase or transposase complex, a cas effector complex comprising a cas effector and at least one engineered guide polynucleotide configured to hybridize to the target nucleic acid site, and the recombinase or transposase complex wherein said recombinase or transposase complex is configured to recruit the cargo nucleotide to the target nucleic acid site.

Abstract: Disclosed herein are zinc finger nucleases for cleaving a CIITA gene, polynucleotides encoding the same, and methods of using the zinc finger nucleases to modulate the expression of a CIITA gene. Also provided is a cell modified by the zinc finger nucleases and uses of the cell to treat a disease.

Abstract: Provided are compositions and methods that include one or more of: (1) a Class 2 CRISPR/Cas effector protein, a nucleic acid encoding the effector protein, and/or a modified host cell comprising the effector protein (and/or a nucleic acid encoding the same); (2) a CRISPR/Cas guide RNA that binds to and provides sequence specificity to the Class 2 CRISPR/Cas effector protein, a nucleic acid encoding the CRISPR/Cas guide RNA, and/or a modified host cell comprising the CRISPR/Cas guide RNA (and/or a nucleic acid encoding the same); and (3) a CRISPR/Cas transactivating noncoding RNA (trancRNA), a nucleic acid encoding the CRISPR/Cas trancRNA, and/or a modified host cell comprising the CRISPR/Cas trancRNA (and/or a nucleic acid encoding the same).

Abstract: Compositions and methods for gene editing are provided. In some embodiments, provided is a polynucleotide encoding an RNA-guided DNA binding agent such as N. meningitidis Cas9 that can provide one or more of improved editing efficiency, reduced immunogenicity, or other benefits.

Abstract: Provided here are, inter alia, methods of estimating a genetic predisposition of an individual subject developing a phenotype by identifying a plurality of different rare genetic variant in a population of subjects and estimating the genetic predisposition of the individual subject developing the phenotype based at least in part on the presence of the plurality of different rare genetic variants within the genome of the individual.

Abstract: Provided herein are compositions, systems, and methods comprising effector proteins and uses thereof. These effector proteins may be characterized as CRISPR-associated (Cas) proteins. Various compositions, systems, and methods of the present disclosure may leverage the activities of these effector proteins for the modification, detection, and engineering of nucleic acids.

Abstract: Polynucleotides including nucleic acids encoding ?-galactosidase A (GLA) are described. Also described are expression cassettes, vectors, cells, and cell lines containing the polynucleotides, as well as methods of using the polynucleotides to treat lysosomal storage disorders such as Fabry disease.

Abstract: The present invention relates, in general, to polypeptides capable of neutralizing SARS-CoV-2 and providing ACE2 enzymatic activity, and uses of these polypeptides for treating disorders related coronaviral infections (COVID-19) and the accompanying acute respiratory distress syndrome (ARDS) and major organ injuries, and methods of making such molecules.

Abstract: The present disclosure is to provide a recombinant botulinum toxin type A light chain, a recombinant botulinum toxin, and a composition, use, and method related thereto, which exhibit improved efficacy and half-life to be easier to use for patients and enable treatment that is customized to indications.

Abstract: The present disclosure provides AprL-clade protease enzymes, including variant AprL-clade protease enzymes, nucleic acids encoding same, and compositions and methods related to the production and use thereof, including an AprL-clade variant subtilisin enzyme that has improved stability and/or soil removal compared to a parent AprL-clade subtilisin enzyme.

Abstract: The present disclosure relates to serine proteases and variants thereof. Compositions containing the serine proteases are suitable for use in cleaning fabrics and hard surfaces, as well as in a variety of industrial applications.

Abstract: Compositions and methods comprising deaminase polypeptides for targeted editing of nucleic acids are provided. Compositions comprise deaminase polypeptides. Also provided are fusion proteins comprising a DNA-binding polypeptide and a deaminase of the invention. The fusion proteins include RNA-guided nucleases fused to deaminases, optionally in complex with guide RNAs. Compositions also include nucleic acid molecules encoding the deaminases or the fusion proteins. Vectors and host cells comprising the nucleic acid molecules encoding the deaminases or the fusion proteins are also provided.

Abstract: The present disclosure relates, in part, to soluble guanylyl cyclase (GC1) mimetic polypeptides comprising amino acid residues 581-635 of the ?-subunit of soluble guanylyl cyclase (GC1), or a fragment thereof, and at least one cell penetrating peptide (CPP). The present disclosure further relates to methods of treating, preventing, and/or ameliorating a disease or disorder in a subject, including but not limited to cancer, hypertension, hypotension, and cardiac dysfunction. In certain embodiments, the methods comprising administering to the subject the polypeptide of the present disclosure.

Abstract: A genetically modified Bacillus subtilis strain has been transformed with an optimized vector, mainly for producing a D-psicose 3-epimerase.

Abstract: Cellulose-based scaffolds for enzyme immobilization and methods for forming and using the scaffolds are described. The scaffolds incorporate delignified bamboo that can be functionalized to include an enzyme immobilized at a surface of the delignified bamboo via an alkylamine linkage. Disclosed scaffolds can be utilized in enzyme-based flow bioreactors.

Abstract: Harvested stem cells are activated by treating them with an amplitude modulated laser beam having a wavelength lying in the range of 405 to 980 nanometers. The frequency of the laser beam is modulated within a range of 8 to 12 MHz. Using the activated stem cells, tissue can be repaired and regenerated by preparing the unactivated stem cells, treating the unactivated stem cells with an amplitude modulated laser beam having a pre-determined frequency for obtaining activated stem cells, administering the activated stem cells into a body containing the tissue, and using a homing beam to guide the activated stem cells within the body to the location of the tissue.

Abstract: An object of the present disclosure is at least to provide a cell fusion method having a high cell fusion rate. The object is solved by a cell fusion method including pressurizing, by a pressurization portion, a solution containing multiple cells of one or more types and at least one type of chemical cell fusion agent, the solution contained in a container portion.

Abstract: Provided are methods, compositions and kits for depleting host nucleic acid in a biological sample, said sample having been previously obtained from an animal host.

Abstract: The present invention provides a method for the isolation of sperm DNA from swabs taken from rape victims without having to perform a change in buffers. Non-sperm cells from the victim are digested with an enzyme and solubilized, and then in the same buffer an enzyme capable of digesting soluble DNA is added and the victim's DNA is degraded, leaving only the rapist's DNA intact. Since no change of buffer is needed, no centrifugation or filtration steps are needed. The inventive method has utility particularly in the forensic science field.

Abstract: The invention relates to various components that make up a system for extracting, purification, analysis and/or detection of nucleic acid molecules. A first component comprises a nucleic acid capturing device adapted for dipping into a liquid wherein a portion of the device contacting the liquid comprises a nucleic acid binding agent. The nucleic acid binding agent may comprise silica (SiO2). The invention also includes a method for producing said nucleic acid capturing device. A second component comprises a grinding device comprising a mortar and pestle with the mortar comprising an upper portion and a base grinding portion. The grinding device enables efficient grinding in the base grinding portion and facilitates access to the addition of materials (e.g. fluids to the base grinding portion) when in use. A third component is an amplification device (e.g. a heating device for isothermal amplification).

Abstract: The invention relates to a device methods and an assembly for isolating biological polymers from a sample, the device comprising a top reservoir, a bottom reservoir, a collection chamber located between the top and the bottom reservoirs and operably connected to the top and bottom reservoirs, a sieving matrix capable of passing the biological polymers to be extracted, a semipermeable membrane not capable of passing the biological polymers to be extracted, and at least one set of a working electrode and a counter electrode.

Abstract: The present disclosure relates to fluidic systems and devices for processing, extracting, or purifying one or more analytes. These systems and devices can be used for processing samples and extracting nucleic acids, for example by isotachophoresis. In particular, the systems and related methods can allow for extraction of nucleic acids, including non-crosslinked nucleic acids, from samples such as tissue or cells. The systems and devices can also be used for multiplex parallel sample processing.

Abstract: The present invention pertains to methods and kits for isolating extracellular nucleic acids from a biological sample using anion exchange particles. It was found that incorporating into the binding mixture a polyoxyalkylene fatty alcohol ether compensates performance variations that are attributable to differences in the anion exchange surface as they may occur e.g. between different lots/batches of the anion exchange particles and/or during storage of said particles. Moreover, including a polyoxyalkylene fatty alcohol ether in the binding mixture resulted in a higher purity of the obtained eluates revealing significantly less inhibition in a downstream reaction such as a PCR reaction.

Abstract: Through a combination of apoptosis, necrosis, and secretion, tumor DNA is released into the bloodstream and becomes part of the cell-free DNA (cfDNA). The present disclosure provides methods, systems, devices, and kits for isolating circulating free DNA (cfDNA) from a biological sample (e.g., plasma) using RNA-guided DNA binding proteins (e.g. Gas proteins.). Particularly, the disclosure provide methods, systems, devices, and kits for Cas9 mediated capture of cfDNA from flowing plasma.

Abstract: Systems, and their methods of use, for sorting or separating magnetic particles are provided. A system having a magnetic module with features that mate with voids in a flow module exerts a magnetic field on magnetic particles to separate particles.

Abstract: Microfluidic apparatuses including concentrators and buffer exchange regions that concentrate and exchange buffer. Also described are methods of passing a solution through a feed channel, filtering small molecules out of the feed channel by tangential flow filtration into a permeate channel adjacent to the first feed channel while maintaining a constant sheer rate relative to the membrane separating the feed channel from the permeate channel and exchanging buffer into the solution and concentrating the solution in a second region of the apparatus.

Abstract: This invention relates to compositions and methods for modifying FACIATED EAR2 (FEA2) genes in plants, optionally to modify meristem size. The invention further relates to plants having increased kernel row number produced using the methods and compositions of the invention.

Abstract: Presented are methods and compositions for using immobilized transposase and a transposon end for generating an immobilized library of 5?-tagged double-stranded target DNA on a surface. The methods are useful for generating 5?- and 3?-tagged DNA fragments for use in a variety of processes, including massively parallel DNA sequencing.

Abstract: This invention relates to a method for codon optimising a target nucleic acid sequence for expression in a host cell. The invention also relates to codon optimised nucleic acids for improved expression in a host cell, and to vectors and host cells comprising codon optimised nucleic acids.

Abstract: This disclosure generally relates to high-throughput and modular methods and compositions for barcode-trackable cellular receptor design, manufacture, and measurement.

Abstract: Described herein is a method of preparing an unbiased library of phage variants, comprising (a) preparing a population of “acceptor phage”; (b) removing an endogenous target gene and inserting gene variants into the acceptor phage genomes; (c) enriching the recombined phages; and (d) expressing the library for selection. The acceptor phage is a lytic phage comprising a synthetic genome wherein the target gene of interest is flanked by recombinase sites. The acceptor phage infects a first host bacteria expressing a recombination plasmid facilitating recombination. The phages then infect a second host bacteria expressing a counterselection system that accumulates recombined phage variants and selecting against non-recombined phages. The accumulated phage variants infect a third host bacteria. The phage library may then be sequenced and characterized.

Abstract: The present invention provides, among other things, a guide RNA conjugated to a NLS sequence (NLS-gRNA) and method for making and using the same. For example, in some embodiments, the 3? end of the gRNA is conjugated to the N-terminus of a nuclear localization sequence (NLS) via a linker comprising a chemical moiety and a peptide spacer.

Abstract: The invention relates to methods for treating subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria, using iRNA, e.g., double stranded ribonucleic acid (dsRNA), compositions targeting the complement component C5 gene, and anti-C5 antibodies, e.g., eculizumab.

Abstract: The present invention relates to a use of a miR-145 inhibitor in preventing aggravation of myocardial infarction or treating myocardial infarction. A miR-145 antagomir reduces ischemic myocardial injury and necrosis upon myocardial infarction and increases the regeneration of myocardial tissues, thereby exhibiting a regenerative therapeutic effect after onset of myocardial infarction. Even when administered alone, the miR-145 antagomir exhibits a similar level of therapeutic effect to that when administered in combination with a miR-124 antagomir, and particularly, brings about a remarkable therapeutic effect at the initial stage (acute phase) within several days after onset of myocardial infarction. Thus, the antagomir can be used for treating myocardial infarction.