Abstract: Methods and structures are disclosed for creating a physical linkage between two or more viral particles, which can covalently link the viral particles together. The methods and structures described herein are designed for purposes of improving efficiency and effectiveness of vector delivery into cells and tissues for purposes of gene therapy. Methods for linking two or more viral vectors comprise functionalizing a first vector with a first surface moiety and functionalizing a second vector with a second surface moiety. Thereafter, the first functionalized vector and second functionalized vector are combined so that the two surface moieties can react. During this reaction, the first surface moiety and the second surface moiety form a covalent linkage, thereby resulting in the physical linkage of both vectors to each other.

Abstract: The present invention relates to a stable method for introducing at least one inducible cassette into a cell, and permitting controllable transcription from within that inducible cassette. The method may be used for any cell type, from any eukaryotic organism, but has a particular application in the introduction of inducible cassettes into pluripotent stem cells, such as animal or human pluripotent stem cells (hPSCs). The inducible cassette is controllably inserted in such a way to ensure that the genetic material it contains is not silenced or subject to negative influences from the insertion site, and transcription of the genetic material is controlled.

Abstract: Disclosed herein are pharmaceutical compositions for delivery of a chimpanzee adenovirus (ChAdV)-based expression system.

Abstract: The systems and methods are directed to leveraging the channel geometry and configuration to overcome diffusion limitations of current transduction systems. The methods may include a method of transducing target cells using a device. The device may include at least one continuous channel. The method may include delivering target cells and viral vectors into a transduction region of the channel. After transducing for some incubation time, a flushing solution may be delivered. The method may include collecting transduced cells after the transducing incubation time and the delivering of the flushing solution.

Abstract: The invention provides a solution to the problem of transfecting non-adherent cells. Devices and delivery compositions containing ethanol and an isotonic salt solution are used for delivery of compounds and compositions to non-adherent cells.

Abstract: The present invention discloses a system for targeted gene editing and related uses.

Abstract: Provided herein, inter alia, are compositions and methods related to correcting intron 22 inversion in the F8 gene using AAVHSC-mediated nuclease-free genome-editing.

Abstract: The present disclosure provides efficient and precise methods and tools for use in the editing of nucleic acid. The disclosure provides a method of editing a nucleic acid comprising cutting or cleaving a nucleic acid to be edited, contacting the cut nucleic acid with a nucleic acid repair template so that the nucleic acid repair template comprises an end which matches a cut end of the nucleic acid to be edited and a sequence that is homologous to a sequence of nucleic acid to be edited.

Abstract: A preparation method for a universal CAR-T cell, and an use of a universal CAR-T cell. When universal CAR-T is prepared, an RNP complex comprises an RNP complex composed of a Cas9 protein and sgRNA; and the SgRNA is SgRNA of CD4 and/or sgRNA of CD8. ?he CD4 gene and/or CD8 gene of the universal CAR-T cell or a T cell are/is knocked out and/or inactivated. The CAR-T cell expresses CD44 and/or CD62L, so that the activity of the CAR-T cell can be enhanced, the effectiveness of CAR-T is enhanced, the CAR-T cell has a better phenotype and lower exhaustion expression, and the killing of the CAR-T cell against a tumor target cell is improved, and thus, the CAR-T cell can be used for targeted therapy of tumors and can be used for allogenic CAR-T therapy.

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

Abstract: The present disclosure discloses a base editor and the use thereof. The present disclosure provides a nucleic acid base editor, specifically a base editor which is not based on CRISPR technology. The base editor comprises a sequence-specific DNA binding protein, a nickase, an exonuclease and a base-specific deaminase. This base editor is single-strand-specific, and as compared with conventional base editors, the base editor of the present disclosure has wide applicability in cells and is capable of functioning in the nucleus as well as in mitochondrial DNA and/or chloroplast DNA. This base editor has the characteristics of achieving base editing products with high purity and resulting in few indel byproducts while realizing efficient base editing, which is conducive to being used as an efficient and safe gene editing tool.

Abstract: A method for increasing the production of Erinacine A in liquid fermentation of Hericium erinaceus is provided. Through screening of exogenous factors, methyl violet and/or rotenone are selected as the exogenous factors, which ultimately greatly increases the Erinacine A content in the liquid fermentation of Hericium erinaceus, with important production and application value. The liquid fermentation method has high efficiency and can significantly increase the content of Erinacine A in the liquid fermentation process, breaking through the synthetic barrier and having the characteristics of large increase amplitude and fast effect. Compared with other current research on liquid fermentation of Hericium erinaceus to produce Erinacine A, the method for increasing the liquid fermentation production of Erinacine A from Hericium erinaceus is at the highest level, with important research significance.

Abstract: The disclosure relates to fatty diols and recombinant microorganisms for producing them. More particularly, the disclosure relates to recombinant microorganisms engineered to produce fatty diols via fermentation. Further encompassed is a process that uses the microorganisms to produce fatty diols from a simple carbon source.

Abstract: Disclosed herein are novel methods and compositions of matter to produce 3HB in acetogens by using a(S)-3-hydroxybutyryl-CoA dehydrogenase, Hbd2, responsible for endogenous 3HB production. In conjunction with the heterologous thiolase atoB and CoA transferase ctfAB, hbd2 overexpression improves yields of 3HB on both sugar and syngas (CO/H2/CO2), outperforming previously disclosed pathways.

Abstract: The present invention relates to the technical field of microbial engineering. Specifically disclosed are a recombinant microorganism, a method for constructing same and use thereof. According to the present invention, by means of constructing a phosphate acetyltransferase-inactivated strain and applying the strain to the production of threonine, the threonine-producing ability of the strain is remarkably improved, and the strain has a remarkably increased production of threonine as compared to an unmodified strain. Combined with attenuated expression or inactivation of acetate kinase, HTH-type transcriptional regulator and the like, as well as improved activity of pyruvate carboxylase and enzymes involved in a threonine synthesis-related pathway, the production of threonine is further improved. The described modifications can be used in the fermentative production of threonine and have relatively good application value.

Abstract: A fermentation process for extracting cannabis-based phytocompounds is described. The process utilizes wine or bear yeasts to ferment cannabis flowers, resulting in cannabis lees enriched with cannabis-based phytocompounds.

Abstract: The present invention relates to the provision of an enzymatic method for the preparation of 2,6-bis(hydroxy methyl)pyridine starting from 2,6-lutidine using a mutated xylene monooxygenase enzyme, termed ppXMO, comprising a xylM subunit and a xylA subunit from Pseudomonas putida, wherein said mutated enzymes harbor an amino acid exchange at position 116 of the amino acid sequence of XylM component. The essence of the invention is that the methionine (M) at this position is replaced with an aminoacid selected in the group consisting of asparagine (N), lysine (K), arginine (R) and glycine (G), which surprisingly results in a direct methyl hydroxylation of 6-methyl-2-pyridine methanol resulting in improved overall process yield, less side products are produced, avoidance of toxic reaction intermediates and minimizing the need for involvement of endogenous reductase enzymes as well as NADPH and its regeneration. Other enzymes related to XylM of P.

Abstract: The present invention provides a method for synthesizing nicotinic acid from 3-picoline using transformed recombinant host cells with synthetically designed gene constructs as whole cell biocatalysts. Adaptive engineering of aromatic ring metabolizing genes isolated from microorganisms enables efficient metabolism of 3-picoline. Mutants with enhanced activity profiles are developed through gene-level modifications, ensuring superior catalytic efficiency and stability. Synthetic biology techniques generate tailored coding sequences for optimum expression. Synthetic constructs embedded with engineered genes, ribosomal binding sites, and spacers are co-expressed within one cellular unit. A one-pot reaction system utilizes versatile plasmid vectors like pET28a(+) for efficient co-expression, advancing the host microorganism matrix. The invention integrates immobilized whole-cell catalysts, addressing catalyst reusability, stability, and industrial scalability.

Abstract: A method for producing glucose and derivatives thereof by means of biotransformation with a recombinant yeast, which belongs to the technical field of synthetic biology. A construction method comprises any one of the following steps: i, knocking out metabolic pathway-related enzymes of glucose and derivatives thereof in a yeast strain; ii, enhancing or using an activity of synthetic pathway-related enzymes of glucose and derivatives thereof in the yeast strain; and iii, enhancing or using a capability of glucose and derivatives thereof in the yeast strain to enter and exit the yeast. Further provided are a recombinant yeast strain capable of producing glucose or derivatives thereof at a high yield and the use thereof in the conversion of a non-grain low-carbon carbon source.

Abstract: The present invention is intended to provide a novel use of a maltotriosyl transferase. The present invention provides a method for producing rice cakes or noodles, including a step of heat-treating a dough containing maltotriosyl transferase thereby gelatinizing starch in the dough. The present invention also provides a method for producing an indigestible saccharide, including a step of allowing maltotriosyl transferase to act on a saccharide.

Abstract: A plurality of terminal deoxynucleotidyl transferases (TdTs) and variants thereof are used for de novo synthesis of polynucleotides having controlled sequences and efficiently controllable synthesis of nucleic acid molecules without depending on a template. It is found that some amino acid residues in the TdT catalytic domain can be specifically modified to improve the ability of such modified TdTs to synthesize polynucleotides.

Abstract: A method for in vitro transcription of a DNA template into RNA includes providing a mixture containing a buffer substance, ribonucleoside triphosphates (NTPs), one or more magnesium salts in a concentration of from about 2 mM to about 60 mM, the DNA template, and a recombinant RNA polymerase, and incubating the reaction mixture at from about 25° C. to about 40° C. for from about 1 hour to about 12 hours thereby producing the RNA. A method for in vitro transcription includes providing a DNA template and a cap analogue that binds to ?1 and/or +1 nucleotides of promoter for in vitro transcription, thus producing more full length mRNAs, allowing for more flexibility on the choice of first mRNA base, and providing+2 position open for custom sequence.

Abstract: The present invention provides, among other things, methods for purifying mRNA based on normal flow filtration for therapeutic use.

Abstract: The present invention relates to a process for generating single-stranded overhangs (sticky ends) of a user-defined length and sequence in a predominantly double-stranded DNA molecule, wherein the process is restriction endonuclease and DNA exonuclease activity-independent and wherein formed heteroduplex DNAs are joined by one or more ligations using a DNA ligase with an end result of generating double-stranded DNA fragments with single-stranded overhangs for joining and generating larger linear or covalently closed circular DNA molecules with the option of variable regions.

Abstract: Thermothelomyces heterothallica (formerly Myceliophthora thermophila) genetically modified to produce glycoproteins with N-glycans of mammalian proteins (particularly human, companion animal and other animal proteins) are provided, comprising deletion or disruption of the alg3 gene, expression of ER-targeted Mannosidase 1 (alpha-1.2-Mannosidase), and expression of ER-targeted Glucosidase 2 alpha-subunit. The Th. heterothallica may also further comprise heterologous GlcNAc transferase 1 (GNT1), GlcNAc transferase 2 (GNT2), STT3 subunit of a heterologous oligosaccharyltransferase and galactosyltransferase.

Abstract: The present disclosure includes an improved method of making a protein. The steps and conditions were described and carried out with significantly improved protein yield, thereby reducing manufacturing cost.

Abstract: Disclosed herein are metabolically engineered cells capable of producing carotenoids from acid whey.

Abstract: Method and composition of stabilizing nicotinamide adenine dinucleotide (NAD) in a biological sample are provided. NAD in the sample is stabilized by contacting the sample collected from a subject with nicotinamide and/or nicotinamide derivative.

Abstract: The present invention relates to a SDFAST (Self Dilution for Faster Antimicrobial Susceptibility Testing), which is a microfluidic device that can perform self-dilution and does not require any pumps or valves to accomplish multiplexed microfluidic processes. SDFAST is designed using AutoCAD and fabricated using micro-milling machine. It consists of two polymethyl methacrylate (PMMA) rectangular plates which are in contact throughout the operation. The first plate is the bottom one that serves as lines of wells. The second plate is the top one that acts as a lid and seals the system. The second plate has complementary designs that echo the wells in the first plate, which allows fluidic channels to be formed.

Abstract: Provided herein are reagent tests that can be used to identify specific types of antibiotic resistant microorganisms in a sample, and methods of use thereof.

Abstract: The disclosure relates to formulations and methods for the in chemico testing of toxins based on a discovery that measuring a reduction in enzyme activity can be used to predict in vivo toxicity, including for example, a skin corrosion, skin irritation, eye corrosion, eye irritation, lung toxicity, liver toxicity, nervous system toxicity, developmental toxicity, acute toxicity etc. Disclosed methods are rapid, easy to perform and shelf-stable approaches for identification of toxic chemicals and materials.

Abstract: The present disclosure relates to a method for screening an acetylcholinesterase inhibitor, and further relates to a kit and system for screening an acetylcholinesterase inhibitor.

Abstract: Method for diagnosing Alzheimer's disease in an individual, comprising the steps of providing at least one serum sample derived from the individual, providing at least one preparation of phage clones expressing peptides that mimic conformational epitopes of the A?-42 peptide, reacting said at least one serum sample with said at least one preparation of phage clones expressing peptides that mimic conformational epitopes of A?-42, so that antibodies that may be present in said serum and are directed against the A?-42 peptide bind to the peptides expressed by phage clones of said preparation of phage clones, detecting, by real-time PCR technique, the quantity of phage clones of said preparation to which said antibodies have bound, and determining, based on the quantity of phage clones of said preparation to which said antibodies have bound, whether the individual from whom said serum sample was derived suffers from Alzheimer's disease.

Abstract: Provided herein is technology relating to identifying the binding locations of DNA-binding proteins and particularly, but not exclusively, to methods, systems, and kits that use affinity reagent-specific barcodes for simultaneously mapping the binding sites of multiple proteins in the same cell.

Abstract: The disclosure provides compositions, methods, and kits that facilitate the characterization of omic variation in tissues while preserving spatial information related to the origin of target analytes in the tissue.

Abstract: Provided herein are methods of analyzing DNA molecules in a sample (e.g.

Abstract: Provided are methods of producing product nucleic acids involving the use of oligonucleotides that are modified by the application of a stimulus. Aspects of such methods may include producing product nucleic acids using de-activatable oligonucleotides that are deactivated by a de-activating stimulus, as well as methods that may include producing product nucleic acids using activatable oligonucleotides that are activated by an activating stimulus and de-activatable oligonucleotides that are deactivated by a de-activating stimulus. Also provided are kits, compositions and devices that include de-activatable oligonucleotides or activatable and de-activatable oligonucleotides, e.g., for use in performing the methods as described herein.

Abstract: The present disclosure relates to methods for high throughput analysis of analytes such as polypeptides in a cyclic manner (e.g., using NGPA or NGPS described herein) that allow adjustment of the dynamic range and sensitivity of analyte detection, for instance, based on the abundances of different polypeptides present in a sample to be analyzed. The approaches proposed herein can be used to adjust the dynamic range of abundant analytes (e.g., polypeptides present in high concentrations) in biological samples, such as plasma samples, and to increase proteome coverage achieved by high throughput protein analysis methods, for instance, by improving the sensitivity of detecting less abundant analytes.

Abstract: The invention relates to a protein having at least 50% sequence identity with SEQ ID NO:1, and its use in in vitro transcription methods. The invention further relates to a nucleic acid molecule encoding the protein and to a host cell expressing the protein.

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: The present invention relates to a method for analyzing the structure of 5? terminus of an RNA molecule in a population of RNA molecules using catalytic nucleic acids, e.g., for determining the presence or absence of a 5? cap structure.

Abstract: Described in various embodiments herein are tiled amplification nucleic acid detection systems and uses thereof. In some embodiments, the nucleic acids amplified and detected are cell free DNA (cfDNA).

Abstract: The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

Abstract: The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

Abstract: This disclosure provides an in situ proximity assay. In some embodiments, the method may comprise (a) performing a proximity assay on one or more pairs of binding agent—oligonucleotide conjugates that are bound to the sample, in situ, to produce proximity assay reaction products; and (b) labeling the sites in the sample at which the proximity assay reaction products are produced, wherein the labeling comprises hybridizing an oligonucleotide to the proximity assay reaction products and does not involve primer extension.

Abstract: Provided herein are methods for determining the mislocalization of an analyte by capturing the analyte on an array and measuring the mislocalization distance.

Abstract: In some examples, a dendritic molecule may include a dendritic core; a seeding primer coupled to the dendritic core; and a plurality of dendrons, each of the dendrons comprising an inert, elongated polymer comprising a first end coupled to the dendritic core and a second end coupled to a first functional group, wherein the first functional group is to react with a second functional group to form a covalent bond. In other examples, a dendritic molecule may include a dendritic core; a single-stranded polynucleotide covalently bonded to the dendritic core; and a plurality of dendrons, each of the dendrons comprising an inert, elongated polymer comprising a first end coupled to the dendritic core and a second end.

Abstract: A PCR kit-of-parts is described. The kit-of-parts comprises a first oligonucleotide bound to a bead by a cleavable linker; a second oligonucleotide bound to a bead by a cleavable linker; and an enzyme bound to a bead by a cleavable linker; wherein the first and second oligonucleotide form an oligonucleotide pair complementary to a nucleic acid of interest and the enzyme is capable of extending nucleic acid strands; and each cleavable linker is independently selected from a photocleavable linker and a thermally cleavable linker. Also described is a method of performing PCR and a PCR system.

Abstract: Provided are methods of analyzing capped ribonucleic acids (RNAs). The methods include translocating an adapted RNA through a nanopore of a nanopore device. The adapted RNA includes an RNA region, a 5? cap, and an adapter polynucleotide attached to the 5? cap. The methods include monitoring ionic current through the nanopore during the translocating, translocating the 5? cap through the nanopore, and identifying one or more ionic current features characteristic of the 5? cap (e.g., a triphosphate linkage between the 5? cap and nucleotide N1 of the RNA region, a 5? to 5? orientation of the 5? cap and nucleotide N1 of the RNA region, and/or the like), translocating through the nanopore. Also provided are computer-readable media, computer devices, and systems that find use, e.g., in practicing the methods of the present disclosure.

Abstract: The present disclosure provides compositions and methods related to TET-assisted Pyridine Borane Sequencing (TAPS). In particular, the present disclosure provides optimized TAPS for cfDNA (cfTAPS), which provides high-quality and high-depth whole-genome cell-free methylomes. The compositions and methods provided herein facilitate the acquisition of multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation for the diagnosis and treatment of disease.