Abstract: The present disclosure provides engineered transaminase enzymes having improved properties as compared to a naturally occurring wild-type transaminase enzyme. Also provided are polynucleotides encoding the engineered transaminase enzymes, host cells capable of expressing the engineered transaminase enzymes, and methods of using the engineered transaminase enzymes to synthesize a variety of chiral compounds.

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

Abstract: The present invention provides PiggyBac transposase proteins, nucleic acids encoding the same, compositions comprising the same, kits comprising the same, non-human transgenic animals comprising the same, and methods of using the same.

Abstract: Provided herein are recombinant polymerases that are suitable for nucleic acid amplification assays. The recombinant polymerases disclosed herein are useful in many recombinant DNA techniques, in particular nucleic acid amplification. Also provided herein are methods of producing the recombinant polymerases.

Abstract: Provided herein are proteins, which are capable of being transported across the blood-brain barrier (BBB) and comprise sulfoglucosamine sulfohydrolase (SGSH) enzyme-Fc fusion polypeptides. Certain embodiments also provide methods of using such proteins to treat Sanfilippo syndrome A.

Abstract: The present disclosure is directed to polypeptides, such as polypeptides comprising an alkaline phosphatase and a bone-targeting moiety. Also disclosed are expression vectors, such as lentiviral expression vectors, including a nucleotide sequence encoding a polypeptide. Also disclosed are methods of treating hypophosphatasia or treating, mitigating, or preventing one or more symptoms of hypophosphatasia by administering to a subject in need of treatment thereof the disclosed polypeptides or host cells transduced to express any of the disclosed polypeptides.

Abstract: The present disclosure relates to variant lipolytic enzymes, more particularly variant lipolytic enzymes that have improved stability and/or improved hydrolytic activity on a polyester. Such variant lipolytic enzymes find use in the degradation of polyesters, such as polyethylene terephthalate. Also provided are compositions and methods related to such variant lipolytic enzymes.

Abstract: The present disclosure relates generally to a polypeptide having mono-(2-hydroxyethyl) terephthalate hydrolase (MHETase) activity, more specifically to a polypeptide comprising an amino acid sequence that (i) has at least 70% sequence identity to SEQ ID NO:1 and (ii) differs from SEQ ID NO:1 by an amino acid substitution at one or more positions selected from the group consisting of positions that correspond to amino acid positions 156 to 396, 398 to 410 and 425 to 603 of SEQ ID NO:1.

Abstract: The invention concerns the targeted genomic modification of a plant cell, preferably a meristem cell. More in particular, the invention pertains to a vector expressing a coding RNA, wherein the coding RNA comprises a sequence encoding a CRISPR-nuclease and a mobile element, wherein the mobile element enables intercellular translocation of the coding RNA, preferably intercellular translocation to a meristem cell. The invention further concerns an editing RNA comprising the coding RNA and further comprising a guide RNA.

Abstract: Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.

Abstract: Provided is a gene for efficiently expressing hyaluronic acid hydrolase. A nucleotide sequence of the gene is represented by SEQ ID NO: 4. By truncating a segment of a signal peptide sequence at the N-terminus of a full-length hyaluronic acid hydrolase gene, the Pichia pastoris engineering strain of high level expression genetic engineering hyaluronic acid hydrolase is constructed. The enzyme activity of the hyaluronic acid hydrolase in a fermentation broth obtained by high-density fermentation using the constructed Pichia pastoris engineering strain is up to 4.7×105 U/mL.

Abstract: The present invention relates to subtilase variants suitable for use in, e.g., cleaning or detergent compositions, such as laundry detergent compositions and dish wash compositions, including automatic dish wash compositions. The present invention also relates to isolated DNA sequences encoding the variants, expression vectors, host cells, and methods for producing and using the variants of the invention.

Abstract: The present invention provides polynucleotide sequences derived from Helichrysum umbraculigerum and encoding a protein or a plurality thereof belonging to the acyl activating enzyme (AAE) family. Further provided are an artificial nucleic acid molecule including the polynucleotide, a transgenic cell, tissue, or plant including same. Further provided are method for synthesizing an acyl coenzyme A (CoA).

Abstract: A recombinant ligase composition including a recombinantly-produced ligase isolated from Acanthocystis turfacea chlorella virus 1 (ATCV-1) fused to at least one polynucleotide-binding polypeptide is provided. Compositions containing the recombinant ligase composition, vectors encoding the recombinant ligase composition, and methods of making and using the recombinant ligase composition are also provided.

Abstract: The present invention relates to the use of glutamine synthetase as a protein therapy (such as enzyme replacement protein therapy) for the treatment of hyperammonemia. In particular the invention relates to the systemic administration of glutamine synthetase. The glutamine synthetase may be provided in conjugated or fusion form, to increase its half-life in the circulation. Also provided is a pharmaceutical composition comprising glutamine synthetase. The invention also relates to the uses, methods, and compositions involving a combination of the glutamine synthetase protein and an ammonia lowering agent, such as a nitrogen scavenger.

Abstract: The present disclosure relates to compositions and methods for inducing encystment of and/or stabilising ciliate cells. In particular, the present disclosure relates to polymers and polymeric solutions, including hydrocolloids, which may be used to induce encystment of trophont ciliate cells to form encysted ciliate cells and/or stabilise encysted cells. The present disclosure also relates to methods of infecting and/or colonising molluscs with the compositions and ciliates described herein.

Abstract: Provided is an acoustic microfluidic system for cell fusion, a preparation method therefor and use thereof, which relates to the technical field of cell fusion. The acoustic microfluidic system of the present invention comprises a signal generator, a power amplifier, a PDMS cavity, a micro-injection pump, a pipeline, an EP tube, a cell recovery container, and a bulk wave transducer/surface acoustic wave transducer. The side wall/bottom of the PDMS cavity is provided with identical microporous structures disposed in a staggered manner The system of the present invention has the advantages of extremely low heat production quantity, simple operation, high repeatability and strong stability, and is suitable for the fusion of homologous cells and non-homologous cells. The system is not only suitable for the fusion of two cells, but also for the fusion of a plurality of cells, and can be widely applied to various types of cells.

Abstract: Provided herein are libraries containing synthetic polynucleotides that encode activatable binding polypeptides. Further provided herein are activatable binding polypeptides and polypeptide libraries containing such activatable binding polypeptides. Also provided herein are vectors, vector libraries, cells, kits, and methods of making and using activatable polypeptide libraries.

Abstract: Isolated antigen binding molecules that specifically binds to a molecule comprising an amino acid sequence selected from the group consisting of GGGS (SEQ ID NO: 1), GGGGS (SEQ ID NO: 46) and related sequences are provided. The antigen binding molecules may be used in the methods provided herein.

Abstract: Provided herein are compositions and methods of use thereof for screening a plurality of uniquely identifiable therapeutic moieties by identifying one or more reporters indicative of a cell state. The methods include the administration of a library of expression cassettes, comprising a plurality of nucleic acid sequences, each encoding a different therapeutic moiety operably linked to a therapeutic moiety barcode; a plurality of nucleic acid sequences encoding one or more reporters that collectively, when expressed in a cell or an isolated nucleus, are indicative of a cell state or a likelihood of a cell state of the cell; and one or more sequences encoding a non-coding nuclear retention RNA motif.

Abstract: Disclosures herein are directed to methods and compositions for the detection of and screening for mutations that convey phenotypic properties in a protein such as, for example, drug-resistance. Embodiments of the present disclosure include lentiviral-based compositions for transferring a gene encoding a protein of interest into a target cell for screening according to methods disclosed herein.

Abstract: Described herein are compositions and methods for preparing double-stranded complementary DNA (cDNA) from RNA. In some embodiments, these methods allow isothermal preparation of cDNA. In some embodiments, these methods allow mesophilic or thermostable preparation of cDNA. Also described herein are compositions and methods for preparing cDNA and a library of double-stranded cDNA fragments in a single reaction vessel.

Abstract: An object of the present invention is to provide an antisense guide RNA for editing a polyadenylation signal sequence of a target RNA and a nucleic acid that encodes the guide RNA, which are expected to control expression of the target RNA with high efficiency. The present inventors have intensively examined technologies for controlling expression of a target RNA with high efficiency, thereby completing the present invention by discovering a guide RNA for ADAR-dependent editing of the target RNA, including an antisense region complementary to a portion of the target RNA including a polyadenylation signal sequence.

Abstract: Methods of modulating regulatory T (Treg) suppressor activity are provided. Also provided are methods of treating autoimmune diseases and methods of treating cancer. The methods include increasing or reducing the expression or activity of bromodomain-containing 9 (Brd9), bromodomain-containing 7 (Brd7), and/or polybromo 1 (Pbrm1) in a Treg cell or in a subject.

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: Provided herein are compositions and methods for treating and/or ameliorating FOXG1 syndrome or the symptoms associated therewith. The compositions and methods disclosed herein utilize antisense oligonucleotides that target FOXG1 in order to modulate FOXG1 by, for example, increasing the amount of FOXG1 (e.g. mRNA encoding a FOXG1 protein or FOXG1 protein) in a cell, thereby restoring FOXG1 function.

Abstract: The present invention relates to a FUBPI inhibitor for use in treatment of an HBV infection, in particular a chronic HBV infection. The invention in particular relates to the use of FUBPI inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to nucleic acid molecules, such as oligonucleotides including siRNA, shRNA and antisense oligonucleotides, which are complementary to FUBPI and capable of reducing a FUBPI mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment and/or prevention of a HBV infection.

Abstract: The present disclosure provides methods of treating an individual having Timothy syndrome. Aspects of the methods include administering an effective dose of an agent to the individual, wherein the agent modulates the splicing of an 8 A or an 8 exon of CACNA1C. Also provided are compositions that find use in practicing embodiments of the methods.

Abstract: Alternative splicing events in SCN1A gene can lead to non-productive mRNA transcripts which in turn can lead to aberrant protein expression, and therapeutic agents which can target the alternative splicing events in SCN1A gene can modulate the expression level of functional proteins in Dravet Syndrome patients and/or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition caused by SCN1A, SCN8A or SCN5A protein deficiency.

Abstract: This disclosure relates to modified guide RNAs comprising an internal linker for in vitro and in vivo gene editing methods.

Abstract: This disclosure provides for methods and reagents for rapid multiplex RPA reactions and improved methods for detection of multiplex RPA reaction products. In addition, the disclosure provides new methods for eliminating carryover contamination between RPA processes.

Abstract: The present invention is directed to Saccharomyces-generated extracellular vesicles (EVs) comprising a foreign RNA molecule or protein and at least one foreign membrane surface exposed ligand that specifically binds to a target receptor displayed on a target cell. The present invention also relates to methods of making and using these Saccharomyces-generated EVs for targeted gene silencing. The present invention also relates to fusion proteins comprising a Saccharomyces extracellular vesicle anchor protein and a second peptide designed to bind to cell-specific receptors.

Abstract: The present disclosure provides for splice-switching oligonucleotides (SSOs) targeted to a nucleic acid encoding a transposable element (TE)-driven isoform of LIN28B, such as AluJb-LIN28B. The SSOs may be targeted to an exon-intron or intron-exon junction to inhibit splicing and expression of the TE-driven isoform of LIN28B. Methods of treating cancer, particularly cancers expressing AluJb-LIN28B, comprising administering the SSOs are also provided.

Abstract: A composition that includes a micro-RNA mimic containing one or more adenine bases in which at least one adenine base is replaced by 6-mercaptopurine. Also provided is a method for killing a cancer cell by contacting it with a composition that includes a micro-RNA mimic containing 6-mercaptopurine and 5-fluorouracil in which the micro-RNA mimic is miR-15a, miR-16, miR-129, miR-194, miR-192, miR-139, miR-140, or miR-145. Further, disclosed is a method for treating cancer by administering a composition containing a micro-RNA mimic having a guide strand and a passenger strand in which at least one adenine base in the guide strand or the passenger strand has been replaced by 6-mercaptopurine.

Abstract: The present invention relates to a multi-conjugate of small interfering RNA (siRNA) and a preparing method of the same, more precisely a multi-conjugate of siRNA prepared by direct binding of double stranded sense/antisense siRNA monomers or indirect covalent bonding mediated by a cross-linking agent or a polymer, and a preparing method of the same. The preparing method of a siRNA multi-conjugate of the present invention is characterized by simple and efficient reaction and thereby the prepared siRNA multi-conjugate of the present invention has high molecular weight multiple times the conventional siRNA, so that it has high negative charge density, suggesting that it has excellent ionic interaction with a cationic gene carrier and high gene delivery efficiency.

Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a SOD1 gene, as well as methods of inhibiting expression of a SOD1 gene and methods of treating subjects having a SOD1-associated neurodegenerative disease or disorder, e.g., Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS), using such dsRNAi agents and compositions.

Abstract: The present invention provides methods for the treatment of non-alcoholic steatohepatitis (NASH) including advanced fibrotic and/or cirrhotic stages of NASH. The methods include administration of a compound comprising a double stranded RNAi (dsRNAi) oligonucleotide, or a pharmaceutically acceptable salt thereof, to the patient. The dsRNAi oligonucleotide optionally contains an antisense strand and a sense strand, wherein the antisense strand and the sense strand form a duplex region, and wherein the antisense strand comprises a region of complementarity to a KHK mRNA target sequence.

Abstract: The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the ketohexokinase (KHK) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a KHK gene and to methods of treating or preventing a KHK-associated disorder in a subject.

Abstract: Compositions, methods and kits are provided that include an inhibitory oligonucleotide RNase inhibitor capable of inhibiting one or more types of RNase that coexist with biological samples or are introduced in the laboratory, thereby protecting RNA in the sample from degradation. More than one type of oligonucleotide RNase inhibitor may be combined in a mixture to inhibit a plurality of different RNases. Single oligonucleotides were identified to have inhibitory activity for a plurality of different RNases. The RNase oligonucleotide inhibitor may be immobilized on beads or other surface. It may be stored in a lyophilized form or in solution.

Abstract: Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a fibrotic cell.

Abstract: Provided herein are compositions including aptamers capable of binding to and/or inhibiting the activity of nucleolin. Methods of treating cancer in a subject by administering such compositions are also provided.

Abstract: Chimeric antigen receptors containing tumor necrosis factor receptor superfamily member transmembrane domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Abstract: The disclosure relates to recombinant host cells including strain modifications effective to improve titer, yield and/or productivity of fatty acid derivatives. The disclosure further relates to cell cultures including the recombinant host cells for the fermentative production of fatty acid derivatives and compositions thereof.

Abstract: This invention provides compositions and methods for providing high product yield of transgenes expressed in cyanobacteria and microalgae.

Abstract: The instant disclosure provides a genetically modified bacterial cell, i.e., modified Agrobacterium strain, which expresses a levansucrase and has reduced expression of endogenous CysK. As a result, the growth of the modified bacterial cell on medium or tissue culture with sucrose and deficient in cysteine is inhibited. The two-action growth control of the modified Agrobacterium strain can overcome the unmet issue of Agrobacterium overgrowth during plant transformation, and therefore increase the efficiency of plant transformation.

Abstract: The present disclosure relates to a recombinant vector for plant expression system in which expression is increased by a radio frequency. According to the present disclosure, since the recombinant vector for plant expression of the present disclosure significantly increased the expression of the target protein in plants by treatment of an eco-friendly and biologically stable radio frequency, there is an effect of overcoming a low protein expression problem of a method using plant cells while having an advantageous effect capable of replacing a conventional production method using animal cells or microorganisms.

Abstract: The present inventions relate to a breeding system for the production of polyploid maize seeds, maize plants, or maize plant parts where cycles of meiosis, syngamy, and selection are used for interpopulation improvement of progenitor lines, and sexual polyploidization occurs during hybrid production by inducing clonal gamete formation in the parents that are to be crossed. Reciprocal recurrent selection can be used to inform selection of candidate maize lines that are either advanced to a gene editing or genetic modification system or crossed and selected to induce clonal gamete formation by arresting meiotic recombination and chromosome reduction. Crosses of parent maize plants bearing clonal gametes are planned and executed based upon predicted heterotic performance at the polyploid level. The final product is a homogeneous population of hybrid polyploid maize seed, or derivative thereof, bearing both parents' complete nuclear genomes.

Abstract: The present invention relates to methods of synthesizing long-chain polyunsaturated fatty acids, especially eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, in recombinant cells such as yeast or plant cells. Also provided are recombinant cells or plants which produce long-chain polyunsaturated fatty acids. Furthermore, the present invention relates to a group of new enzymes which possess desaturase or elongase activity that can be used in methods of synthesizing long-chain polyunsaturated fatty acids. In particular, the present invention provides ?3 destaurases, ?5 elongases and ?6 desaturases with novel activities. Also provided are methods and DNA constructs for transiently and/or stably transforming cells, particularly plant cells, with multiple genes.

Abstract: The present invention relates to methods of synthesizing long-chain polyunsaturated fatty acids, especially eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, in recombinant cells such as yeast or plant cells. Also provided are recombinant cells or plants which produce long-chain polyunsaturated fatty acids. Furthermore, the present invention relates to a group of new enzymes which possess desaturase or elongase activity that can be used in methods of synthesizing long-chain polyunsaturated fatty acids. In particular, the present invention provides ?3 destaurases, ?5 elongases and ?6 desaturases with novel activities. Also provided are methods and DNA constructs for transiently and/or stably transforming cells, particularly plant cells, with multiple genes.

Abstract: The present invention relates to methods of synthesizing long-chain polyunsaturated fatty acids, especially eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, in recombinant cells such as yeast or plant cells. Also provided are recombinant cells or plants which produce long-chain polyunsaturated fatty acids. Furthermore, the present invention relates to a group of new enzymes which possess desaturase or elongase activity that can be used in methods of synthesizing long-chain polyunsaturated fatty acids. In particular, the present invention provides ?3 destaurases, ?5 elongases and ?6 desaturases with novel activities. Also provided are methods and DNA constructs for transiently and/or stably transforming cells, particularly plant cells, with multiple genes.