Abstract: The disclosure provides Myxoma viruses that express one or more multi-specific immune cell engagers, such as BiKE, BiTE and/or MiTE and their use in inhibiting and/or treating a hematological cancer in a subject. The disclosure also provides a leukocyte having a Myxoma virus that expresses one or more multi-specific immune cell engagers, and the use of the leukocyte for inhibiting and/or treating a hematological cancer in a subject.

Abstract: The present invention relates to virus-like particles (VLPs) having a high affinity protein attachment system which allows interchangeable decoration with any functional molecule of choice. The present invention further relates to processes of producing the VLPs, including a rapid single cell process, and uses of the VLPs in research, diagnosis and as vaccines for use in prevention/treatment of diseases.

Abstract: A method of targeting cancer tissue in a subject includes administering to the subject a plurality of functionalized Tymovirus virus or virus-like particles loaded with or conjugated to an imaging agent, a therapeutic agent or a targeting agent.

Abstract: A simian adenoviral vector comprising two expression cassettes, wherein each expression cassette comprises a transgene and a promoter, and wherein the first expression cassette is inserted in the E1 region of the simian adenoviral vector, and the second expression cassette is inserted in a region of the adenoviral vector that is compatible with vector replication.

Abstract: Immobilized proteases for activation of the zymogen form of transglutaminase are disclosed.

Abstract: The present application relates to an aroG aldolase (phospho-2-dehydro-3-deoxyheptonate aldolase) variant, a microorganism comprising the same, and a method for producing amino acids using the same.

Abstract: The present invention relates to a polymerase enzyme from 9° N with improved ability to incorporate reversibly terminating nucleotides. The enzyme comprising mutations in the motif A region. The invention also relates to methods of using such enzymes as well as a kit with such polymerases.

Abstract: The present invention is directed to terminal deoxynucleotidyltransferase (TdT) variants that (i) comprise an amino acid sequence that is at least a specified percent identical to an indicated SEQ ID NOs and have at least one substitution at Q455 or at least Q455 plus at least one further substitution at G186, S248, T331, Q390, K394 or H466 (where positions are with respect to SEQ ID NO 1 and functionally equivalent positions in indicated SEQ ID NOs), (ii) are capable of template-free extension of a polynucleotide, and (iii) exhibit enhanced stability or enhanced efficiency in incorporating 3?-0-blocked nucleoside triphosphates into a polynucleotide. The invention is also directed to the use of these TdT variants for synthesizing polynucleotides of any predetermined sequence.

Abstract: The present invention provides several non-naturally occurring sulfotransferase enzymes that have been engineered to react with aryl sulfate compounds as sulfo group donors, instead of the natural substrate 3?-phosphoadenosine 5?-phosphosulfate (PAPS), and with heparosan-based polysaccharides, particularly heparan sulfate, as sulfo group acceptors. Each of the engineered sulfotransferase enzymes have a biological activity characterized by the position within the heparosan-based polysaccharide that receives the sulfo group, including glucosaminyl N-sulfotransferase activity, hexuronyl 2-O sulfotransferase activity, glucosaminyl 6-O sulfotransferase activity, or glucosaminyl 3-O sulfotransferase activity. Methods of using the engineered sulfotransferases to produce sulfated heparosan-based polysaccharides, including polysaccharides having anticoagulant activity, are also provided.

Abstract: Provided are an esterase mutant and use thereof. The amino acid sequence of the esterase mutant has a sequence as shown in SEQ ID NO: 1, and sites at which amino acid mutations occur include an N51G site.

Abstract: The invention provides a CRISPR-dCas/Cas protein derivative or CRISPR-dCas/Cas protein derivative set derived from a CRISPR-dCas (dead Cas) protein or a CRISPR-Cas protein, as well as a polynucleotide encoding the same, a vector comprising the polynucleotide, a transformant transformed by the vector, a carrier for purifying a target RNA, a method for purifying a target RNA, a method for analyzing an intracellular environment, and a prophylactic or therapeutic agent.

Abstract: The present invention provides for a synthetic transcription factor (TF) comprising (a) a DNA-binding domain of a transcription factor linked to (b) an effector domain, and (c) optionanlly a nuclear localization sequence (NLS). The present invention provides for a nucleic acid encoding an effector domain of the present invention. The DNA-binding domain can be a deactivated RNA-guided nuclease variant of Cas9 (dCas9).

Abstract: The present invention relates to polypeptide having alpha-amylase activity. The present invention also relates to polynucleotides encoding the polypeptides; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the polypeptides.

Abstract: A chimeric lysozyme variant has an improved heat resistance and is encoded by a polynucleotide. A novel chimeric lysozyme sequence is constructed, and high-efficiency expression in a host cell is achieved. The thermal stability of the chimeric lysozyme under the condition of 60° C. is nearly doubled compared to a parental sequence. The chimeric lysozyme variant can be used to prepare product that is antibiotic, for example, animal feed additive containing the chimeric lysozyme variant and an animal feed containing the animal feed additive.

Abstract: The present invention relates to compositions comprising at least two polypeptides having mannanase activity as well as methods of producing and using the compositions. The compositions comprise in particular a first mannanase which is a glycoside hydrolase family 5 (GH5) mannanase and a second mannanase which a glycoside hydrolase family 26 (GH26) mannanase.

Abstract: Provided herein are methods for treating or preventing infection of a subject by a virus that infects the subject through angiotensin converting enzyme 2.

Abstract: Certain disclosed embodiments concern a bioremediation composition comprising microbial cells, at least one co-metabolism substrate to induce selected enzyme production by the microbial cells, and a bead or gel encapsulating the microbial cells, such as bacterial or fungi cells, and the at least one co-metabolism substrate. For certain embodiments, the substrate is a slow release compound, such as an orthosilicate that hydrolyzes to produce an alcohol growth substrate. Embodiments of a method for using the composition to transform contaminants of concern also are disclosed.

Abstract: The present invention relates to methods of increasing metabolic activity and stimulating cell proliferation of biological cells through the use of pulsed electric field (PEF) treatment, especially through the use of nanosecond pulsed electric field (nsPEF) treatment.

Abstract: An automatic loading system for an extraction strip includes: an extraction strip for holding several reagents, a first channel, a second channel parallel to and attached to the first channel, a first hand pushing device for pushing the extraction strip to move in the first channel, a second hand pushing device for pushing the extraction strip to move in the second channel, and a transfer device for transferring the extraction strip from the first channel to the second channel. One end of the first channel is a loading inlet of the extraction strip. One end of the second channel is a grabbing position of the extraction strip. The transfer device is arranged at the other ends of the first channel and the second channel. The first hand pushing device and the second hand pushing device can move transversely and move up and down.

Abstract: This disclosure provides compositions and methods for high throughput screening, selecting, and identifying antibodies or antibody-like molecules that bind to a target integral membrane protein.

Abstract: Aspects of the invention described herein relate to methods of making and using inducible promoters for transgene expression. The inducible promoters are derived from the NFAT-RE inducible system and are used to improve or enhance T cell survival and proliferation.

Abstract: Described here are VHH antibody libraries with heavy chain variable domains framework scaffolds having complementary determining regions (CDRs) found in naturally-occurring human antibodies, and methods of making such antibody libraries. The antibody libraries are free of members that comprise one or more liabilities affecting one or more features of such members.

Abstract: The invention relates to a method of preparing a nucleic acid library from a sample comprising high molecular weight DNA (HMW DNA), preferably genomic DNA, comprising the steps (i) contacting said DNA with a first restriction enzyme and a second restriction enzyme; (ii) contacting said DNA with a pair of oligonucleotide adapters according to any of claims 1 to 12; (iii) contacting said DNA with at least one DNA ligase; and (iv) incubating to allow digestion of the DNA by said first restriction enzyme and second restriction enzyme, annealing of said oligonucleotide adapters to the digested DNA, and ligation of the annealed oligonucleotide adapters to the digested DNA by said at least one DNA ligase. The invention also relates to oligonucleotide adapters, a kit, and uses of same.

Abstract: The present invention pertains to methods for obtaining captured polynucleotide fragments. Further provided are methods for obtaining rearranged captured polynucleotide fragments. The present invention also relates to methods for the identification of at least one compound, at least one protein, and/or at least one secondary metabolite having biological activity. Kits for performing the above methods, methods of treatment using the compounds as screened with the methods for identification of at least one compound having biological activity, as well as pharmaceutical compositions thereof, are also provided.

Abstract: A method for isolating a mammalian genomic DNA replication origin, the method including: isolating the genomic DNA molecules; identifying 500 bp windows within the DNA molecules; isolating from the genomic DNA molecules the fragments that have a size from 500 pb up 6000 pb; selecting a DNA replication origin that is able, when contained in the DNA of an Eukaryotic cell, to produce nascent DNA, and to initiate DNA replication; and isolating the origin.

Abstract: The present disclosure relates to the methods and systems for multimodal profiling. The method can include stabilizing a target, performing a tagmentation on the target using an agent, and generating a library using a reverse transcriptase enzyme. The agent can include a Tn5 transposome complex, a Tn5 transposase reagent, or a combination thereof, and the Tn5 transposome complex or the Tn5 transposase reagent can be loaded with an adapter. The reverse transcriptase enzyme can be configured to transcribe DNA from both a DNA template and an RNA template and perform a terminal transferase activity by template switching and an introduction of an adapter sequence into a cDNA and a transposed chromatin of the target.

Abstract: Compositions and methods are provided for the reversible modification of RNA to enhance RNA in-solution and enzymatic stability by reaction with acylimidazoles, sulfonyltriazoles, or sulfonylimidazoles. 2?-OH acylation protects RNA from hydrolytic and enzymatic degradation. Water-soluble organocatalysts can accelerate the reversal of acylation adducts and functionally restore RNAs, alternatively the acylation is spontaneously reversed in a cellular environment. Chemically tuned 2?-OH acylation can be spontaneously released in cells to restore RNA biological functions including translation. mRNA can be selectively modified at the 2?-OH of poly(A)-tail for enhanced in-cell stability and enhanced total protein output.

Abstract: DNA molecules for making a circular RNA are provided. The DNA molecule may include elements operably connected and arranged, from a 5? to 3? direction, in the following order: (a) an intron fragment that includes a full-length intron; (b) an E2 fragment which includes a downstream exon of the full-length intron; and (c) an E1 fragment which includes an upstream exon of the full-length intron. 3? end of the E1 fragment is configured to produce a hydroxyl group in an in vitro transcription reaction; the hydroxyl group is capable of initiating splicing in a one-step transesterification reaction at a splice site between RNA fragments transcribed from the intron fragment and the E2 fragment in a linear RNA that is produced from the DNA molecule in the in vitro transcription reaction, such that the linear RNA is configured to self-circularize to produce the circular RNA.

Abstract: The disclosure provides, e.g., compositions, systems, and methods for targeting, editing, modifying, or manipulating a host cell's genome at one or more locations in a DNA sequence in a cell, tissue, or subject. Gene modifying systems for treating cystic fibrosis, e.g., in subjects having a mutation resulting in F508del, are described.

Abstract: A technology that may be used to program ribosomes to synthesize specific proteins and rejuvenate tissues and include the ability to modulate or program the function of ribosomes towards a specific desired function, such as for use with tissue rejuvenation and the production of missing or mutated proteins.

Abstract: The present disclosure relates to an RNAi-inducing nucleic acid molecule and use thereof. An aspect of the disclosure relates to an RNAi-inducing nucleic acid molecule for inhibiting expression of myeloid differentiation primary response gene 88 (MyD88). Another aspect of the present disclosure relates to a pharmaceutical composition for treating or preventing age-related macular degeneration, compri the RNAi-inducing nucleic acid molecule.

Abstract: The present disclosure provides vector stuffer polynucleotides and compositions thereof, including expression constructs and vectors, such as viral vectors and methods of delivering a therapeutic agent (e.g., inhibitory nucleic acid) to a mammal or treating a disease.

Abstract: The present disclosure provides compositions and methods for inhibiting viral pathogenesis by targeting long noncoding ribonucleic acids.

Abstract: Disclosed herein are products, methods, and uses for treating, ameliorating, delaying the progression of, and/or preventing a muscular dystrophy or a cancer including, but not limited to, facioscapulohumeral muscular dystrophy (FSHD) or a cancer associated with DUX4 expression or overexpression. More particularly, disclosed herein are RNA interference-based products, methods, and uses for inhibiting or downregulating the expression of double homeobox 4 (DUX4). Even more particularly, the disclosure provides microRNA (miRNA) for inhibiting or downregulating the expression of DUX4 and methods of using said miRNA to inhibit or downregulate DUX4 expression in cells and/or in cells of a subject having a muscular dystrophy or a cancer including, but not limited to, FSHD or a cancer associated with DUX4 expression or overexpression.

Abstract: Provided herein are compositions and methods for treating and/or ameliorating the FOXG1 syndromes or the symptoms associated therewith. The compositions and methods disclosed herein utilize antisense oligonucleotides that target long non-coding RNAs (lncRNAs) to increase FOXG1 expression in a cell, thereby restoring FOXG1 function.

Abstract: The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are stmctural information on the Cas protein of the CRISPR-Cas system, use of this information in generating modified components of the CRISPR complex, vectors and vector systems which encode one or more components or modified components of a CRISPR complex, as well as methods for the design and use of such vectors and components. Also provided are methods of directing CRISPR complex formulation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. In particular the present invention comprehends optimized functional CRISPR-Cas enzyme systems.

Abstract: The present invention belongs to the technical field of biomedicine, and mainly relates to a miR-7-5p mimic for inhibiting migration and invasion of breast cancer, a screening method and an application thereof. The sequence of the miR-7-5p is shown in SEQ ID NO.1. The present invention has found that the miR-7-5p mimic generates a significant inhibitory effect on breast cancer through targeted inhibition of the molecular mechanism of RYK. In vitro culture system, the miR-7-5p mimic can function to inhibit migration and invasion capabilities of breast cancer. The miR-7-5p mimic can inhibit RYK protein and mRNA levels in breast cancer. In nude mice, the miR-7-5p mimic can also significantly inhibit migration and invasion capabilities of breast cancer. Therefore, the present invention demonstrates that the miR-7-5p mimic can be a small-nucleic-acid drug to significantly inhibit breast cancer metastasis.

Abstract: Some embodiments of the invention include a nucleic acid molecule comprising natural nucleotides, non-natural nucleotides, an LNA which comprises one or more RNA core molecules, or an RNA molecule which comprises more than one RNA core molecule. Some embodiments of the invention include a nucleic acid molecule comprising an RNA molecule which comprises more than one RNA core molecule. Other embodiments of the invention include a nucleic acid molecule comprising a DNA molecule encoding the RNA molecule (e.g., vector or viral vector). Other embodiments include compositions or pharmaceutical compositions that comprise the nucleic acid molecule. Some embodiments of the invention comprise reducing miR-143 in a cell. Other embodiments of the invention include methods to deliver a protein across the BBB. Other embodiments include methods for treating disease (e.g., LSD), neuronopathic disease, neurodegenerative disease, Hurler syndrome, or MPS I). Additional embodiments of the invention are also discussed herein.

Abstract: The present invention provides methods and compositions for stable genetic modification of cultured mammalian cells. The genetic modifications can be used to produce cultured mammalian cells for therapeutic or diagnostic purposes.

Abstract: Disclosed herein polynucleotides complementary to IL-34, including IL-34 antisense oligonucleotides and IL-34 NAs, and methods for treating inflammatory diseases, such as an inflammatory bowel disease, and/or fibrosis, associated with elevated activity or expression of IL-34. Also disclosed are pharmaceutical compositions containing a polynucleotide complementary to IL-34, for example, an IL-34 antisense oligonucleotide or an IL-34 siRNA, useful for treating inflammatory diseases and/or fibrosis and manufacture of medicaments containing a disclosed polynucleotide to be used in treating inflammatory diseases and/or fibrosis.

Abstract: This invention relates to methods, compositions, kits and uses of medicaments for treating or ameliorating the symptoms of age disease in a human or animal, or for treating or ameliorating the symptoms of a viral disease, or for inhibiting or suppressing entry or replication of a virus in a cell, or for suppressing an inflammatory response or a cytokine storm. These purposes can be achieved with formulations of agents for inhibiting or suppressing expression of TGF-?. More particularly, this invention discloses compositions, methods and uses for anti-TGF-? agents, such as antisense oligonucleotides against TGF-?, artemisinin, or a combination thereof, in a regimen for age disease.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the PCSK9 gene (PCSK9 gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PCSK9 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier and method for treating diseases caused by PCSK9 gene expression.

Abstract: Provided herein are compositions and methods for improving immune system function. In particular, provided herein are compositions, methods, and uses of YY1 and EZH2 inhibitors for preventing and reversing T-cell exhaustion (e.g., for use in immunotherapy).

Abstract: Provided herein are compositions and methods for non-parenteral delivery of conjugated oligomeric compounds. In certain embodiments, compositions and methods are provided for oral delivery of conjugated oligomeric compounds. In certain embodiments, the oligomeric compounds are conjugated to one or more N-acetylgalactosamines or N-acetylgalactosamine analogues.

Abstract: Methods and materials for treating a mammal having a congenital disease (e.g., a congenital heart disease such as congenital long QT syndrome) are provided herein. For example, this document provides methods and materials for generating and using nucleic acids to treat a mammal having a congenital disease, where the nucleic acids can suppress expression of mutant disease-related alleles in the mammal while providing a replacement cDNA that does not contain the disease-related mutation(s).

Abstract: The present invention includes compositions and methods for treating an autoimmune disorder or a cancer in a subject in need thereof, the method comprising: administering an effective amount of a composition comprising an oligonucleotide that specifically binds a complementary sequence of the Interleukin-7 receptor (IL7R) pre-mRNA that influences splicing of exon 6, wherein the SM-ASO increases or decreases inclusion of exon 6 in IL7R pre-mRNAs and respectively decreases or increases expression of the soluble isoform of IL7R (sIL7R). In certain embodiments, the oligonucleotide is an antisense oligonucleotide (ASO), or a splice-modulating antisense oligonucleotide (SM-ASO).

Abstract: The present invention includes compositions and methods for treating an autoimmune disorder or a cancer in a subject in need thereof, the method comprising: administering an effective amount of a composition comprising an oligonucleotide that specifically binds a complementary sequence of the Interleukin-7 receptor (IL7R) pre-mRNA that influences splicing of exon 6, wherein the SM-ASO increases or decreases inclusion of exon 6 in IL7R pre-mRNAs and respectively decreases or increases expression of the soluble isoform of IL7R (sIL7R). In certain embodiments, the oligonucleotide is an antisense oligonucleotide (ASO), or a splice-modulating antisense oligonucleotide (SM-ASO).

Abstract: Disclosed are aptamers designed to bind immunological checkpoint molecules while concurrently suppressing tumor associated gene expression through delivery of DNA molecules encoding short hairpin DNA. In one embodiment the invention provides an aptamer capable of binding PD-1 and/or PD-1 ligand while concurrently possessing ability to induce RNA interference to one more multiple other immune inhibitory and/or oncogenesis related genes. In one embodiment such a dual-targeting aptamer is utilized to induce systemic tumor abscopal effect.

Abstract: A system for stable expression of gene pathways in cell lines, methods of making cell lines with stable expression of gene pathways, and methods of using the same are disclosed herein. The system comprises a nucleic acid construct configured to encode at least two genes of a multigene pathway in a cell. The nucleic acid construct comprises a plurality of nucleic acid sequences, wherein the plurality of nucleic acid sequences comprises: a first nucleic acid sequence encoding at least one gene of the multigene pathway; a first protease recognition nucleic acid sequence encoding a protease recognition site; a first linker nucleic acid sequence encoding a linker region, wherein the linker region comprises a viral 2A peptide; and a second nucleic acid sequence encoding at least one gene of the multigene pathway.

Abstract: Compositions related to engineered Cas9 enzyme in reducing cellular toxicity and methods using thereof related to the selective targeting and editing endogenous nucleic acid segment in both normal cell and in cell associated with genetic diseases are disclosed. In some cases, a polypeptide comprising a human Exo1 enzyme or a first functional fragment thereof and a Cas9 enzyme or a second functional fragment thereof, which are connected by a linker peptide, is disclosed. In some cases, a polynucleotide encoding the polypeptide and a guide RNA (gRNA) is disclosed. Further, methods for treating single gene disorders utilizing either the polypeptide or the polynucleotide are disclosed.