Abstract: The present invention relates to the field of genetic engineering, particularly to a method for efficiently expressing pullulanase in Bacillus subtilis and recombinant Bacillus subtilis. said method includes steps of constructing modified Bacillus subtilis strain with deletion of alkaline protease gene and neutral protease gene, constructing expression vector including an optimized combination of promoter and signal peptide and pullulanase gene, and transforming said modified Bacillus subtilis strain with by said expression vector. A series of combinations of promoter and signal peptide are optimized to obtain the combination for efficiently expressing pululanase, provide an industrial application basis.

Abstract: Modified Factor IX (FIX) polypeptides, nucleic acid encoding the same, and methods of generating modified Factor IX polypeptides are provided. Also provided are pharmaceutical compositions that contain the modified Factor IX polypeptides, methods of treatment using modified Factor IX polypeptides, and assay for Factor IX activity.

Abstract: The present invention relates to a method for the recombinant production of a serine protease comprising (a) culturing a host cell comprising one or more vectors, wherein the one or more vectors encode in expressible form the serine protease and a proteinaceous inhibitor of the serine protease, wherein the proteinaceous inhibitor of the serine protease is heterologous with respect to the serine protease, under conditions wherein the serine protease and the proteinaceous inhibitor of the serine protease are expressed; or (a?) culturing a host cell the genome of which encodes in expressible form the serine protease and a proteinaceous inhibitor of the serine protease, wherein the proteinaceous inhibitor of the serine protease is heterologous with respect to the serine protease, and wherein the coding sequences of the serine protease and/or the proteinaceous inhibitor have been introduced into the host cell genome by applying a CRISPR technology, under conditions wherein the serine protease and the proteinaceous

Abstract: Provided herein are fusion proteins useful in a bipartite cytosine base editor system comprising: (i) a first fusion protein comprising a non-R-loop-forming programmable DNA binding domain, preferably a transcription-activator-like effector (TALE) or zinc finger array (ZF), fused to a deaminase enzyme, or an active portion thereof, optionally with a linker therebetween, or (ii) a second fusion protein comprising an R-loop-forming Cas9 protein that lacks nuclease activity or is a nickase, but can interact with a guide RNA and target DNA, fused to a Uracil glycosylase inhibitor (UGI), optionally with a linker therebetween. Additionally, provided are methods for targeted deamination of one or more selected cytosines in a nucleic acid.

Abstract: A method for monomerization of MMP-7 aggregates is provided. A method for monomerization of MMP-7 aggregates which comprises treating MMP-7 aggregates with a buffer solution comprising a monovalent cation chloride (sodium chloride, potassium chloride, etc.) at a low concentration or with a buffer solution not comprising a monovalent cation chloride, a process for preparing MMP-7 which involves said method for monomerization, and a (pharmaceutical) composition comprising MMP-7 in the aforementioned buffer solution. In case that a (pharmaceutical) composition comprising MMP-7 at a low concentration is prepared, the aforementioned buffer solution comprising sugar alcohols or sugars is used.

Abstract: The present invention relates to a CRISPR nanocomplex for nonviral genome editing, a method for preparing the same, and the like. The CRISPR nanocomplex for nonviral genome editing of the present invention has a size of several nanometers to several microns, enables intracellular delivery without external physical stimulation, and can be utilized for genome editing through nonviral routes with respect to target genes of cells. As a result, when used for preparation of animal model, microbiological engineering, cell engineering for disease treatment, or formulations for biological administration, the CRISPR Nanocomplex shows high intracellular delivery and gene editing efficiency, and can minimize problems, such as nonspecific editing, gene mutation, and induction of cytotoxicity and biotoxicity.

Abstract: A method for activating a cell-signaling pathway of interest in a cell, including applying a time-modulated localized alternating current electrical field to the cell, wherein the amplitude and frequency of the localized alternating current electrical field is selected to activate the cell signaling pathway of interest, thereby activating the cell signaling pathway.

Abstract: Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.

Abstract: Provided are compositions, methods, and kits for improving CRISPR-based editing of DNA targets by a CRISPR-associated (Cas) enzyme. The improvement is made by combining the Cas enzyme and a CRISPR targeting RNA a heterologous DNA repair enzyme that is at least one of RecBCD, AddAB, or AdnAB. The heterologous DNA repair enzyme may have inactivated nuclease activity. The method can include using a DNA repair template to introduce one or more changes into the edited DNA. Cells that contain components of the improved CRISPR systems are included, as are kits for making such cells.

Abstract: Methods of sequencing and assembling a nucleic acid sequence from a nucleic acid sample containing repetitive or low-information regions, which are typically difficult to sequence and/or assemble are provided. The methods of sequencing and assembling introduce mutations into the sample to increase sequence diversity between various repetitive regions present in the nucleic acid sample. This sequence diversity allows various segments to assemble independently of different, but similar sequences present in the nucleic acid sample.

Abstract: A data storage medium is disclosed comprising a two-dimensional (2D) support structure onto which artificially synthesized DNA molecules encoding digital information are placed and then covered with a protective layer. The 2D support structure is formed from a material such as metal foil, glass, or plastic. The 2D support structure may be functionalized with positively charged molecules to improve DNA adhesion. The DNA is protected from degradation by encapsulation in a protective layer of a non-reactive material such as silica or a thin layer of metal. A process for storing DNA on 2D support structures is also disclosed. Correlation of specific DNA molecules with a physical storage location on a 2D support structure provides geometric addressability for selective access to specific digital information.

Abstract: Methods, kits and compositions for separation, identification, and isolation of short nucleic acids (i.e., less than 100 nucleotides) of different length are provided. The invention further provides methods for preparation of small RNA libraries.

Abstract: The Invention provides in vivo selection methods for identifying modulating agents (e.g., antibodies or polypeptides) that promote cellular differentiation and migration. The methods utilize a combinatorial agent library (e.g., antibodies expressed via lentiviral vectors) that are expressed in a population of to-be modulated cells (e.g., stem cells), which are then introduced into, the body of a non-hum an animal (e.g., mouse). This is followed by examining an organ or tissue of interest (e.g., brain) of the manipulated animal for the presence of a modulating agent and/or a specific phenotype. The; invention also provides specific antibody agent, that can induce differentiation of stem cells into microglia and migration into the brain. Further provided in the invention are therapeutic applications of the microglia-inducing antibodies.

Abstract: The disclosure provides methods of making a protein having a desired non-standard amino acid incorporated at its N-terminus in a cell and methods of screening for an amino acyl tRNA synthetase variant that preferentially selects a non-standard amino acid against its standard amino acid counterpart or undesired non-standard amino acids for incorporation into a protein in a cell.

Abstract: The invention relates to a glycopolypeptide that includes one or more modified amino acid residues having a sidechain comprising a monosaccharide or an oligosaccharide, wherein the glycopolypeptide binds specifically to a carbohydrate-binding monoclonal antibody with an affinity of less than 100 nM. Immunogenic conjugates that include the glycopolypeptide, and pharmaceutical compositions that include the glycopolypeptide or the immunogenic conjugate are also disclosed. Various method of using the glycopolypeptides, immunogenic conjugates, and pharmaceutical compositions are disclosed, including inducing an immune response, inhibiting viral or bacterial infection, treating a cancerous condition, and detecting a neutralizing antibody.

Abstract: Methods for gene targeting or targeted insertion in cells. The methods and compositions described herein can be used to identify the relative frequency of donor molecule integration.

Abstract: Methods, systems, kits and compositions are described for quality control and quantitation of nucleic acid libraries of double stranded nucleic acid libraries prior to massively parallel sequencing. Electrophoretic separation within a channel using a detectably labeled single stranded sizing ladder may be used to define the molecular weight range and amount of the double stranded nucleic acids.

Abstract: A cell model for in vitro evaluation of compound-induced skin sensitization and a constructing method therefor. The method for constructing the cell model comprises the steps of: designing and constructing an sgRNA expression vector based on CRISPR/Cas9 vector system; designing and constructing a homologous recombinant vector capable of knocking a reporter gene linked to a self-cleaving peptide sequence into a specific site of the expression frame of the HMOX1 gene; co-transfecting the homologous recombinant vector, an hCas9 plasmid and the sgRNA expression vector into a cell, and carrying out monoclonal expansion to obtain the cell model. The present invention obtains a HaCaT cell model in which a luciferase gene is knocked in before the stop codon of the HMOX1 gene by combination of CRISPR/CAS9 and a monoclonal cell technique. The cell model realizes synchronous expression of the luciferase gene and the HMOX1 gene, thereby effectively distinguishing sensitizing compounds from non-sensitizing compounds.

Abstract: The current invention provides for methods and medicaments that apply oligonucleotide molecules complementary only to a repetitive sequence in a human gene transcript, for the manufacture of a medicament for the diagnosis, treatment or prevention of a cis-element repeat instability associated genetic disorders in humans. The invention hence provides a method of treatment for cis-element repeat instability associated genetic disorders. The invention also pertains to modified oligonucleotides which can be applied in method of the invention to prevent the accumulation and/or translation of repeat expanded transcripts in cells.

Abstract: Described herein are guide RNAs and modified guide RNAs suitable for biallelic correction of Pompe disease. Also included are methods of modifying a target gene in a patient or in a patient-derived cell, wherein the patient has an autosomal recessive disorder with compound heterozygous mutations, the methods including delivering a first modified guide RNA, a second modified guide RNA, a Cas9 polypeptide, a biotin-binding molecule, a first biotinylated donor polynucleotide, and a second biotinylated donor polynucleotide. The first modified guide RNA and the first biotinylated donor polynucleotide correct a first diseased allele, and the second modified guide RNA and the second biotinylated donor polynucleotide correct a second diseased allele.

Abstract: Novel mIR-330 agents and their methods of use are provided. Methods of treating MYC-associated cancers are provided.

Abstract: The present invention relates to a compound inhibiting the expression and/or the activity of a long non-coding RNA (lncRNA) selected from GADLOR 1 and GADLOR 2 for use in treating or preventing cardiac remodelling, wherein GADLOR 1 comprises or consists of a nucleic acid sequence selected from the group consisting of SEQ ID NOs 1 to 3 and sequences being at least 75% identical thereto, and GADLOR 2 comprises or consists of a nucleic acid sequence selected from the group consisting of SEQ ID NOs 4 to 6 and sequences being at least 75% identical thereto.

Abstract: There are provided polynucleotides that is able to bind to and inhibit the long non coding RNA transcript SCAT7. These polynucleotides can be used for the treatment of cancer. Expression analysis of SCAT7 can be used for diagnosis of cancer.

Abstract: Provided are a therapeutic and/or prophylactic agent for a lung disease and a method for screening for the therapeutic and/or prophylactic agent. Provided are a therapeutic and/or prophylactic agent for a lung disease comprising an Arid5A inhibitor as an active ingredient and a method for screening for the therapeutic and/or prophylactic agent.

Abstract: The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group.

Abstract: The present invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the hepatitis B virus (HBV) genome, and methods of using such RNAi agents to inhibit expression of one or more HBV genes and methods of treating subjects having an HBV infection and/or HBV-associated disorder, e.g., chronic hepatitis B infection.

Abstract: Methods of eliminating a retrovirus from a subject utilize nanoformulated anti-retroviral compounds and gene editing agents. Compositions comprise at least one anti-retroviral compounds, at least one gene-editing agent, or combinations thereof.

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

Abstract: The present invention relates to compositions and methods for the treatment of myotonic dystrophy.

Abstract: This present invention compositions and methods of treating cancer and methods of accessing/monitoring the responsiveness of a cancer cell to a therapeutic compound.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting PNPLA3 expression, which may be useful for treating, preventing, or ameliorating a disease associated with PNPLA3.

Abstract: Methods of treating a wound in a subject are provided comprising administering to the subject an amount of an inhibitor of Fidgetin-like 2. Compositions and pharmaceutical compositions comprising an amount of an inhibitor of Fidgetin-like 2 are also provided. Methods are also provided for identifying an inhibitor of Fidgetin-like 2.

Abstract: The invention relates to methods of inhibiting the expression of a PCSK9 gene in a subject, as well as therapeutic and prophylactic methods for treating subjects having a lipid disorder, such as a hyperlipidemia using RNAi agents, e.g., double-stranded RNAi agents, targeting the PCSK9 gene.

Abstract: A synthetic cDNA which encodes a protein wherein at least one optimal or non-optimal codon in a wild type DNA encoding the protein has been replaced respectively with one or more non-optimal codons or optimal codons encoding the same amino acid.

Abstract: A method for assembling two or more types of vectors includes introducing the two or more types of vectors into a methanol-utilizing yeast strain. The methanol-utilizing yeast strain comprises a DNL4 gene that is inactivated, and the two or more types of vectors are assembled in a transformant of the methanol-utilizing yeast strain.

Abstract: Disclosed herein are plants exhibiting a semi-dwarf phenotype with reduced plant height compared to control wildtype plants. Some of the disclosed semi-dwarf plants comprise at least one non-natural brachytic mutation in which the activity of a BR2 gene is reduced. Also disclosed are methods for producing a semi-dwarf corn plant using a CRISPR based genome editing system.

Abstract: The present technology provides targeted genome engineering (also known as genome editing) techniques to modify nicotine biosynthesis. In particular, the present technology relates to the use of genome editing methods to generate mutations resulting in an out-of-frame start codon upstream of the open reading frames (ORFs) of genes of interest, such as nicotine biosynthesis genes, to genetically engineer protein translation levels and modulate nicotine production in plants for producing plants and plant cells having reduced nicotine content.

Abstract: The present invention is concerned with the provision of means and methods for gene expression. Specifically, it relates to a polynucleotide comprising an expression control sequence which allows for seed specific of a nucleic acid of interest being operatively linked thereto in plants. Furthermore, vectors, host cells, transgenic plants and methods for expressing nucleic acids of interest are provided which are based on the said polynucleotide.

Abstract: The invention provides methods of engineering plants to modulate hydroxycinnamic acid content. The invention additionally provides compositions and methods comprising such plants.

Abstract: A tobacco arsenic transport gene NtNIP7-1 and a cloning method and application thereof are disclosed. A nucleotide sequence of the tobacco arsenic transport gene NtNIP7-1 is shown as SEQ ID: No. 1, and an encoded amino acid sequence thereof is shown as SEQ ID: No. 2. The cloning method of the tobacco arsenic transport gene NtNIP7-1 includes (S1) extracting RNA in tobacco, performing reverse transcription, and obtaining a first-strand cDNA; and (S2) taking the first-strand cDNA obtained by the reverse transcription as a template, synthesizing a specific primer according to sequences of the NtNIP7-1 gene, performing PCR amplification, recovering and purifying a product of the PCR amplification, and sequencing. In the present invention, inhibition of the expression of the tobacco endogenous gene NtNIP7-1 in tobacco plants is able to significantly reduce the arsenic content of tobacco leaves, and has broad application prospects in the field of low arsenic content breeding.

Abstract: A land plant is disclosed. The land plant has increased expression of a mitochondrial transporter protein such that the flux of metabolites through the mitochondrial membrane is increased and the land plant has higher performance and/or yield as compared to a reference land plant not having the increased expression of the mitochondrial transporter protein. Another land plant also is disclosed. The land plant has increased expression of a plastidial dicarboxylate transporter protein such that the flux of metabolites through the plastidial membrane is increased and the land plant has higher performance and/or yield as compared to a reference land plant not having the increased expression of the plastidial dicarboxylate transporter protein.

Abstract: Compositions and methods for improving plant growth are provided herein. Polynucleotides encoding ERF transcription factor proteins, polypeptides encompassing ERF transcription factor proteins, and expression constructs for expressing genes of interest whose expression may improve agronomic properties including but not limited to crop yield, biotic and abiotic stress tolerance, and early vigor, plants comprising the polynucleotides, polypeptides, and expression constructs, and methods of producing transgenic plants are also provided.

Abstract: Methods and materials for modulating low-nitrogen tolerance levels in plants are disclosed. For example, nucleic acids encoding low nitrogen tolerance-modulating polypeptides are disclosed as well as methods for using such nucleic acids to transform plant cells. Also disclosed are plants having increased low-nitrogen tolerance levels and plant products produced from plants having increased low-nitrogen tolerance levels.

Abstract: The disclosure provides nucleic acids, and variants and fragments thereof, derived from strains of Bacillus thuringiensis encoding variant polypeptides having increased pesticidal activity against insect pests, including Lepidoptera and Coleopteran. Particular embodiments of the disclosure provide isolated nucleic acids encoding pesticidal proteins, pesticidal compositions, DNA constructs, and transformed microorganisms and plants comprising a nucleic acid of the embodiments. These compositions find use in methods for controlling pests, especially plant pests.

Abstract: The present disclosure provides a rice planthopper-sensitivity gene BGIOSGA015651 and the use thereof. The applicant found a gene BGIOSGA015651 for regulating rice planthopper-resistance by studying on rice varieties BG1222 and TN1. The gene expression level of BGIOSGA015651 in the insect-resistant variety is hundreds of times or more different from that of the insect-susceptible variety. The expression of this gene can be reduced or knocked out by molecular breeding methods or genetic engineering methods, resulting in that the insect-susceptible plant can obtain high insect-resistance. The resistance level of the insect-susceptible rice variety TN1 is of level 9 before knock-out, and the resistance level thereof is significantly increased to level 0-1 after the rice planthopper-sensitivity gene BGIOSGA015651 is knocked out.

Abstract: The present invention relates to the prevention and/or control of infestation by insect pest species. In particular, the invention relates to down-regulation of expression of target genes in insect pests using interfering ribonucleic acid (RNA) molecules. Also described are transgenic plants that (i) express or are capable of expressing interfering RNAs of the invention and (ii) are resistant to infestation by insect pest species. Compositions containing the interfering RNAs of the invention are also provided.

Abstract: Described herein are embodiments relating to manipulation of populations and sex ratio in populations through DNA sequence modifications.

Abstract: There is provided inter alia an isolated polynucleotide, wherein the polynucleotide encodes a polypeptide selected from the group consisting of: (a) a polypeptide having the amino acid sequence according to SEQ ID NO: 1, (b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 80% identical over its entire length to the amino acid sequence of SEQ ID NO: 1, and (c) a polypeptide having the amino acid sequence according to SEQ ID NO: 3.

Abstract: The present disclosure relates to viral delivery of RNA utilizing self-cleaving ribozymes and applications of such, including but not limited to CRISPR-Cas related applications.

Abstract: Disclosed herein are CMV vectors that include a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), an active UL128 protein (or ortholog thereof), but wherein the CMV vector lacks an active UL130 protein (or an ortholog thereof). Also disclosed herein are CMV vectors comprising: a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), an active UL130 protein (or an ortholog thereof), but wherein the CMV vector lacks an active UL128 protein. Further disclosed are methods of using CMV vectors to generate an immune response characterized as having at least 10% of the CD8+ T cells directed against epitopes presented by MHC Class II.