Abstract: The disclosure relates to compositions and methods of treating mild cognitive impairment in a subject.

Abstract: Provided is a small activating RNA used for promoting an expression level of a target gene. The small activating RNA is composed of a sense oligonucleotide chain and an antisense oligonucleotide chain. A nucleotide of the sense or antisense oligonucleotide chain has 2?-fluoro, 2?-methoxy, and a phosphorothioate modification to the nucleotide backbone.

Abstract: This disclosure relates to novel HTT-1A targeting sequences. Novel HTT-1A targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of APP RNA in a cell or a subject, and in certain instances reducing the amount of APP protein in a cell or a subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease or disorder associated with APP. Such symptoms and hallmarks include cognitive impairment, including a decline in memory and language skills, behavioral and psychological symptoms such as apathy and lack of motivation, gait disturbances, seizures, progressive dementia, and abnormal amyloid deposits.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 RNA in a cell or animal, and in certain embodiments reducing the amount of ATXN3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation formation, and neuron death. Such neurodegenerative diseases include spinocerebellar ataxia type 3(SCA3).

Abstract: Compositions and methods for the treatment of ribosomopathies and regeneration of hematopoietic stems cells are provided.

Abstract: The present invention provides novel highly potent antisense oligonucleotides. Such compounds are useful for making pharmaceutical compositions for treatment of a range of diseases where modulation of miR-134 activity is beneficial, including neurological diseases such as epilepsy.

Abstract: Provided are oligomeric compounds and pharmaceutical compositions for increasing the amount or activity of UNC13A RNA in a cell or animal, and/or decreasing the amount of UNC13A RNA that includes a cryptic exon in a cell or animal, and in certain instances increasing the amount of UNC13A protein in a cell or animal. Such oligomeric compounds and pharmaceutical compositions are useful to treat neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia.

Abstract: Herein, a combination of antisense oligomers or pharmaceutically acceptable salts thereof, or hydrates thereof which cause simultaneous skipping of any two or more numerically consecutive exons selected from the group consisting of the 45th exon to the 55th exon in human dystrophin pre-mRNA is provided.

Abstract: Described herein are compositions and methods useful for detecting and treating pathologies associated with ATF in hepatocytes. A method of detecting a condition, a method of inhibiting a protein, a method of inhibiting a gene, and a method of treatment are disclosed herein. The present disclosure includes, but is not limited to, the development and testing of Atf6-specific short, synthetic, single-stranded antisense oligodeoxynucleotides (ASOs) in vitro and in vivo and future screening for ATF6 inhibitors.

Abstract: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a Filamin A (FLNA) gene, as well as methods of inhibiting expression of an FLNA gene and methods of treating subjects having an FLNA-associated N disease or disorder, e.g., Alzheimer's disease, using such dsRNAi agents and compositions.

Abstract: Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a disease which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

Abstract: A method of increasing or decreasing expression of a target mRNA and protein for treatment of certain disease conditions by cells having a pre-mRNA that comprises a poison exon and encodes the target protein, and can include contacting the cells with an antisense oligomer (ASO) complementary to a targeted portion of the pre-mRNA.

Abstract: This disclosure relates to isolated oligonucleotides comprising duplex regions targeting human complement C3 mRNA, and delivery systems, kits and compositions comprising the same, and methods of using the same for inhibiting or downregulating C3 gene expression.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of Tau mRNA in a cell or animal, and in certain instances reducing the amount of Tau protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disease. Such symptoms include loss of memory, loss of motor function, and increase in the number and/or volume of neurofibrillary inclusions. Such neurodegenerative diseases include tauopathies, Alzheimer's Disease, Fronto-temporal Dementia (FTD), FTDP-17, Progressive Supranuclear Palsy (PSP), Chronic Traumatic Encephalopathy (CTE), Corticobasal Ganglionic Degeneration (CBD), Epilepsy, and Dravet's Syndrome.

Abstract: The present invention relates to methods and compositions comprising an inhibitor of KLF11 signaling for treatment of gastrointestinal motility disorders, obesity and diabetes.

Abstract: The present invention relates to an artificially manipulated immune system having an improved immune effect. More particularly, the present invention relates to an immune system having functions artificially altered which comprises artificially manipulated immunoregulatory elements and cells containing the same.

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: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a leucine-rich repeat kinase 2 (LRRK2) gene, as well as methods of inhibiting expression of a LRRK2 gene and methods of treating subjects having a LRRK2-associated disease or disorder, e.g., Parkinson's disease, using such dsRNAi agents and compositions.

Abstract: The present invention includes a method of treating a bone disease caused by a intracellular protein trafficking defect comprising: identifying a subject having the bone disease caused by the intracellular protein trafficking defect in a membrane bound transcription factor peptidase, site 1 (MBTPS1) gene; and providing the subject with an effective amount of a composition that bypasses or corrects a defect in MBTPS1 gene expression, gene splicing, or corrects protein trafficking defects in the endoplasmic reticulum and to the lysosome.

Abstract: The invention is directed to one or more antisense polynucleotides and their use in pharmaceutical compositions in a strategy to induce exon skipping in the ?-sarcoglycan gene in patients suffering from Limb-Girdle Muscular Dystrophy-20 (LGM-D)2C) or in patients at risk of such a disease. The invention also provides methods of preventing or treating muscular dystrophy, e.g., LGMD)2C, by exon skipping in the gamma sarcoglycan gene using antisense polynucleotides. Accordingly, in some aspects the in-vention provides an isolated antisense oligonucleotide, wherein the oligonucleotide specifically hybridizes to an exon target region of a ?-sarcoglycan RNA. In another aspect, the invention provides a method of inducing exon-skipping of a gamma sarcoglycan RNA, comprising delivering an antisense oligonucleotide or a composition to a cell.

Abstract: Described herein are compositions and methods for modulating cellular senescence of a cell or induction of the senescence-associated secretory phenotype (SASP) in a cell. The methods generally comprise modulating the level or activity of IRE1a as a mean to control cellular senescence and induction of the SASP. Also described are methods for treating and preventing ocular vascular diseases comprising contacting cells in an eye of a subject with a biguanide compound and ophthalmic compositions comprising a biguanide compound.

Abstract: The disclosure relates, in some aspects, to chemically-modified double stranded nucleic acid molecules that are directed against a gene encoding T cell Immunoreceptor with Ig and ITIM domains (TIGIT).

Abstract: The present disclosure relates to a polymer-coated gold nanoparticle-aptamer nanoconstruct having reactive oxygen species sensitivity and capable of treating inflammatory diseases through reactive oxygen species scavenge and TNF-? capture.

Abstract: The present invention provides a simple and inexpensive system for regulating signal peptide performance by using a synthetically evolved nucleotide sequence. The invention further relates to an expression vector comprising the nucleotide sequence. Additionally, the present invention relates to host cell comprising the expression vector. Furthermore, the present invention relates to a recombinant protein expressed by the host cell as well as a method for expressing the recombinant protein.

Abstract: Provided is an isolated polynucleotide including a nucleotide sequence coding for a non-natural 5-untranslated region (5?-UTR) and a nucleotide sequence coding for a non-natural or natural 3-untranslated region (3?-UTR). As such, the polynucleotide increases mRNA stabilization and translation efficiency and thus can be used for effectively acquiring a desired polypeptide.

Abstract: Herein we demonstrate that mitochondrial DNA (mtDNA) influences temperature tolerance in Saccharomyces yeasts. The present invention provides methods for manipulating the mitotype of yeast, including methods to produce synthetic yeast hybrids with a selected mitotype and methods to exchange the native mtDNA present in polyploid yeast with mtDNA from a desired source. Saccharomyces cerevisiae x Saccharomyces eubayanus hybrids with selected mitotypes are also provided. The yeast and methods of the present invention may be utilized in a variety of applications, including in fermentation to produce beer and wine.

Abstract: The invention provides novel compositions and methods for improving the transformation of monocot seed excised embryo explants, which may include one or more steps of explant preparation, explant rehydration, Rhizobiales bacterium inoculation and co-culture, bud induction, extended bud induction, or regeneration of genetically modified plants or plant parts. The methods provided herein may include transforming at least one plant cell of the embryo explant with a heterologous polynucleotide by inoculating the embryo explant with a Rhizobiales bacterium comprising the heterologous polynucleotide. The methods provided herein also include methods of regenerating a genetically modified plant or plant part from a transformed or edited plant cell or explant.

Abstract: Provided herein are genome edited plants and plant parts that comprise increased amino acid content. In particular, the amino acids include tryptophan (Trp) and methionine (Met). Seed of the genome edited plants and plant parts can comprise increased Trp and/or Met. The genome edited plants and plant parts have genetic mutations in an anthranilate synthase gene including a gene encoding an alpha subunit of anthranilate synthase and/or a homocysteine S-methyltransferase gene. The genome edited plants and plant parts include soybean and pea. Also provided herein are compositions and methods of producing such plants and plant parts, and plant products including compositions comprising increased Trp and/or Met content.

Abstract: Method of increasing protein content in a eukaryotic cell comprising an NF-YC4 gene comprising modifying the transcriptional repressor binding site; method of producing a plant with increased protein content comprising crossing and selecting for increased protein content; method of increasing resistance to a pathogen or a pest in a plant cell or plant comprising an NF-YC4 gene comprising modifying the transcriptional repressor binding site, alone or in further combination with expressing QQS in the plant cell or plant; method for producing a plant with increased resistance to a pathogen or a pest comprising crossing and selecting for increased resistance to the pathogen or the pest; a cell, collection of cells, tissue, organ, or organism, such as a plant, in which the NF-YC4 gene comprises a promoter comprising a transcriptional repressor binding site that has been modified so that the transcriptional repressor cannot prevent transcription of the NF-YC4; plants and hybrids thereof; and seeds.

Abstract: This invention relates to compositions and methods for modifying a BRASSINAZOLE-RESISTANT 1 (BZR1) gene in plants to improve yield traits. The invention further relates to plants and plant parts produced using the methods and compositions of the invention.

Abstract: The invention relates to lettuce plants comprising in its genome a mutant homoserine kinase allele in homozygous form, whereby the plants are resistant against Bremia lactucae.

Abstract: Provided herein are regulatory elements, such as transcriptional enhancers, introns, and terminators derived or obtained from various sources including Zea mays and plant viruses. Such regulatory elements are useful for expression cassettes for plants, including monocots (e.g., maize) and dicots (e.g., soy). Enhancers which increase gene expression of tissue specific promoters while maintaining tissue specific expression are provided.

Abstract: A pesticidal protein class of PirA, PirB, and PirAB fusion proteins exhibiting toxic activity against Coleopteran, Lepidopteran, and Hemipteran pest species is disclosed. DNA constructs are provided which contain a recombinant nucleic acid sequence encoding the PirA, PirB, and PirAB fusion proteins. Transgenic plants, plant cells, seed, and plant parts resistant to Coleopteran, Lepidopteran, and Hemipteran infestation are provided which contain recombinant nucleic acid sequences encoding the PirA, PirB, and PirAB fusion proteins. Methods for detecting the presence of the recombinant nucleic acid sequences or the proteins of the present invention in a biological sample, and methods of controlling Coleopteran, Lepidopteran, and Hemipteran species pests using the PirA, PirB, and PirAB fusion proteins are also provided.

Abstract: Methods and compositions are provided for integrating coding sequences for antigen-binding proteins such as broadly neutralizing antibodies into a safe harbor locus such as an albumin locus in an animal in vivo.

Abstract: The present invention provides recombinant adenoviral vectors, immunogenic compositions thereof and their uses in medicine. In particular, the present invention provides an adenoviral vector comprising the genome of an adenovirus other than AdHu5 and AdY25, wherein the genome of the adenovirus has been modified such that the vector lacks the native E4 locus of the adenovirus and comprises heterologous E4Orf1, E4Orf2 and E4Orf3 coding regions from AdY25.

Abstract: Provided herein are compositions and methods of using prime editing systems comprising prime editors and prime editing guide RNAs for treatment of genetic disorders such as cystic fibrosis.

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

Abstract: The disclosure describes Cas12i2 fusion proteins, methods, and compositions for the manipulation of nucleic acids in a targeted fashion. The disclosure describes non-naturally occurring, engineered Cas12i2 fusion proteins, components, and methods for targeted modification of nucleic acids. Each system, includes one or more protein components and one or more nucleic acid components that together target nucleic acids.

Abstract: A method for inhibiting aberrant splicing in a Stathmin-2 (STMN2) transcript, the method comprising: genetically editing a STMN2 gene in a cell to delete (a) one or more nucleotides in a 3? splice site of intron 1, wherein the 3? splice site is adjacent to exon 2a, (b) one or more nucleotides in a region of intron 1 that is adjacent to the 3? splice site, or both (a) and (b), thereby inhibiting production of STMN2 transcripts including exon 2a and improving production of functional STMN2 transcripts in the cell. Also provided herein are gene editing systems for genetic modification of the STMN2 gene.

Abstract: Recombinant Zymomonas mobilis for producing ethylene glycol, method and uses thereof are provided. The recombinant Zymomonas mobilis carries and expresses genes related to a synthesis pathway of xylonic acid and genes related to a synthesis pathway of ethylene glycol.

Abstract: The present invention includes systems, methods and compositions for the in vivo bioconversion of water-soluble cannabinoid glycosides in cell cultures.

Abstract: The present disclosure relates to a novel method for preparing poly(3-hydroxybutyrate-co-4-hydroxybutyrate), a microorganism using the biosynthetic pathway of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) of the present disclosure, a composition for producing poly(3-hydroxybutyrate-co-4-hydroxybutyrate), and a method for regulating the 4-hydroxybutyrate content of poly(3-hydroxybutyrate-co-4-hydroxybutyrate).

Abstract: A method for increasing the oil yield in an ethanol production process comprising: adding a liquid enzyme formulation having at least one enzyme, a buffering agent, a stabilizer, and a preservative where the pH of the enzyme formulation is about pH 6.0-8.0 to a beer, a distillation, a whole stillage, a centrifugation, a thin stillage, an evaporator, a syrup, or an oil recovery unit.

Abstract: Methods for the production of L-glufosinate (also known as phosphinothricin or (S)-2-amino-4-(hydroxy(methyl)phosphonoyl)butanoic acid) are provided. The methods comprise a two-step process. The first step involves the oxidative deamination of D-glufosinate to PPO (2-oxo-4-(hydroxy(methyl)phosphinoyl)butyric acid). The second step involves the specific amination of PPO to L-glufosinate, using an amine group from one or more amine donors. By combining these two reactions, the proportion of L-glufosinate in a mixture of L-glufosinate and D-glufosinate can be substantially increased.

Abstract: The present invention relates to the field of chemical manufacture. In particular, it relates to a method for manufacturing racemic methylglycinediacetic acid (MGDA) comprising the steps of contacting a solution comprising or being enriched in D-alanine or L-alanine to an alanine racemase at a temperature of at least 50° C. and alkaline conditions for a time sufficient to allow conversion of said solution into a racemic alanine solution, obtaining a racemic alanine solution, and chemically converting the racemic alanine into racemic MGDA. The invention further contemplates an alanine racemase which is capable of converting a solution comprising or being enriched in D-alanine or L-alanine into racemic alanine solution at a temperature of at least 50° C. and under alkaline conditions as well as the use of said alanine racemase for converting a solution comprising or being enriched in D-alanine or L-alanine into racemic alanine solution at a temperature of at least 50° C. and under alkaline conditions.

Abstract: Disclosed is a method for producing phycocyanobilin by use of a recombinant Escherichia coli that express heterologous heme oxygenase ho1 and ferredoxin oxidoreductase pcyA derived from Synechocystis sp. PCC6803. According to the present disclosure, heterologous expression of ho1 and pcyA genes leads to conversion of heme to an intermediate biliverdin for phycocyanobilin synthesis, and reduces the accumulation of biliverdin in the process of the phycocyanobilin synthesis. The genome of E. coli is further engineered to overexpress related genes of a metabolic pathway of phycocyanobilin, and a strain of recombinant E. coli with high yield of phycocyanobilin is obtained. The recombinant E. coli strain is cultured for 36 hr in a system using glycerol as a substrate, and the phycocyanobilin yield can reach 147 mg/L.

Abstract: The disclosed technology reduces the force required to consolidate a biomass feedstock into a dense, durable biomass plug having low permeability. The technology increases the fiber density and reduces gas permeability. These changes render the biomass more suitable for seal formation, significantly reducing the force required to form a low-permeability seal. Some variations provides a method of feeding a lignocellulosic biomass feedstock to a biomass-processing unit, comprising: providing a lignocellulosic biomass feedstock; introducing water, in the form of steam and/or liquid water, forming a water-enriched feedstock; feeding the water-enriched feedstock to a plug-forming system to generate a biomass plug of compressed water-enriched feedstock; and conveying the compressed water-enriched feedstock to a biomass-processing unit in flow communication with the plug-forming system.

Abstract: An object of the present invention is to provide a method for producing a fucose-containing carbohydrate more efficiently as compared with that in related art. The present invention relates to any one protein of [1] a protein consisting of the amino acid sequence represented by SEQ ID NO: 2 or 4, [2] a mutant protein having an ?1,3-fucosyltransferase activity and consisting of an amino acid sequence in which 1 to 20 amino acids are deleted, substituted, inserted, or added in the amino acid sequence represented by SEQ ID NO: 2 or 4, and [3] a homologous protein having an ?1,3-fucosyltransferase activity and consisting of an amino acid sequence having an identity of 90% or more with the amino acid sequence represented by SEQ ID NO: 2 or 4.

Abstract: The present disclosure describes compositions and methods useful for the template independent enzymatic synthesis of nucleic acids.