Abstract: Methods for determining a location of a feature in a spatial array with features include: (a) providing an array with a first set of one or more features immobilized on a substrate, a first feature of the first set having a first barcoded oligonucleotide with a first spatial barcode and a first constant sequence, and a second set of one or more features immobilized on the substrate, a second feature of the second set having a second barcoded oligonucleotide with a second spatial barcode and a second constant sequence; (b) attaching the first constant sequence to the second constant sequence to generate a nucleic acid product; (c) determining all or a portion of a sequence of the nucleic acid product or a complement thereof; and (d) associating the second barcoded oligonucleotide with the first barcoded oligonucleotide in the nucleic acid product.

Abstract: The disclosure provides for methods to form compact cross-linked polynucleotide/protein structures that can then be labeled using a barcoded oligonucleotide array in order to reconstruct physical linkage and/or genomic proximity (and phase) of polynucleotide fragments.

Abstract: Methods and compositions are provided for making and using uniquely tagged target nucleic acid molecules.

Abstract: The invention relates generally to tRNA-based effector molecules and methods relating thereto.

Abstract: There is provided a method for suppressing protein expression, including using an oligomer for RNA having first, second, third, and fourth guanine repeat sequences (referred to as “first G sequence,” “second G sequence,” “third G sequence,” and “fourth G sequence,” respectively), the oligomer hybridizing with regions proximal to the guanine repeat sequences, so as to bring the guanine repeat sequences closer together, thereby forming a guanine-quadruplex structure.

Abstract: Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.

Abstract: Aspects of the present invention include methods and compositions related to the modulation of molecules regulating the regenerative potential of cells and tissues in the embryonic state and the loss thereof in later fetal and adult stages of development. Said methods and compositions have uses in research in stern cell biology and in increasing regenerative potential in fetal and adult tissues otherwise incapable of regeneration.

Abstract: The invention relates to a single-stranded antisense gapmer oligonucleotide comprising at least one dinucleoside of formula (I) wherein (A1), (A2) and A are as defined in the description and in the claims. The oligonucleotide according to the invention can be used as a medicament.

Abstract: The present invention provides compositions for RNA interference and methods of use thereof. In particular, the invention provides small interfering RNAs (siRNAs) having modification that enhance the stability of the siRNA without a concomitant loss in the ability of the siRNA to participate in RNA interference (RNAi). The invention also provides siRNAs having modification that increase targeting efficiency. Modifications include chemical crosslinking between the two complementary strands of an siRNA and chemical modification of a 3? terminus of a strand of an siRNA. Preferred modifications are internal modifications, for example, sugar modification, nucleobase modification and/or backbone modifications. Such modifications are also useful, e.g., to improve uptake of the siRNA by a cell. Functional and genomic and proteomic methods are featured. Therapeutic methods are also featured.

Abstract: The invention relates to RNA editing oligonucleotides that are capable of bringing about specific editing of a target nucleotide (adenosine) in a target RNA molecule in a eukaryotic cell, wherein said oligonucleotide is for use in the treatment of Usher syndrome, and more preferably for the deamination of target adenosines that are part of a premature stop codon present in the USH2A pre-mRNA or USH2A mRNA.

Abstract: The invention provides non-opioid pain therapeutic compositions that include an antisense oligonucleotide (ASO) complementary to an identified target on a NaV channel mRNA. The ASO hybridizes to its target RNA and forms a duplex that recruits RNase H to degrade the RNA, thereby downregulating NaV channel synthesis, which inhibits the neuron's ability to contribute to the perception of pain. The ASO targets one of the specific identified targets, and may be provided as a gapmer that includes a central DNA segment flanked by modified RNA wings. When the composition is delivered to dorsal root ganglion (DRG) neurons in vitro, the DRG neurons exhibit a dose-dependent knockdown of NaV1.7, NaV1.8, or NaV1.9.

Abstract: Disclosed herein are systems and methods for identifying candidate targets that may be used for therapeutic developments. The systems and methods may comprise receiving and analyzing biologically relevant data to identify information or events such as splicing events that may be statistically significant or specific to certain diseases, illnesses or conditions. Also provided are systems and methods for modulating the statistically significant events using compositions or molecules including small molecule compounds, oligonucleotides, proteins or cells.

Abstract: Disclosed are methods of diagnosing and treating metastatic cancer in a subject. The methods involve detecting or modulating the expression of at least one of Kif3b, ACTB, SRPK1, TM EM 229b, C14orf142, KB-1460A1.5, ACTC1, Nr2f1, KIAA0922, KDELR3, APBA2, miRNA 130b, miRNA 374b, or miRNA 122 in a biological sample from the subject.

Abstract: The present invention relates inter alia to aptamers that specifically bind to Imatinib and methods of using the same.

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: Provided are immunostimulatory bacteria and oncolytic viruses, and pharmaceutical compositions containing the bacteria and/or viruses, that act as three prime repair exonuclease 1 (TREX1) antagonists. The bacteria and viruses are for treating tumors that are human papillomavirus (HPV) positive or that have a high tumor mutational burden (TMB). The immunostimulatory bacteria and oncolytic viruses encode therapeutic products such RNAi, such as shRNA and microRNA, that mediate gene disruption and/or inhibit expression of TREX1, or that inhibit TREX1. The bacteria contain additional modifications to enhance their anti-tumor activity. The bacteria and viruses are used for treatment of tumors in which TREX1 expression correlates with the presence of the tumor or properties of the tumor, such that inhibition of TREX1 advantageously treats the tumor.

Abstract: Provided herein are methods, compounds, and compositions for reducing expression of GYS1 in an individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a glycogen storage disease or disorder in an individual in need.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of PMP22 RNA in a cell or animal, and in certain instances reducing the amount of PMP22 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 demyelination, progressive axonal damage and/or loss, weakness and wasting of foot and lower leg muscles, foot deformities, and weakness and atrophy in the hands. Such neurodegenerative diseases include Charcot-Marie-Tooth disease.

Abstract: The invention provides compositions and methods for allele specific gene editing. In particular, the invention provides methods and compositions for treating dominant progressive hearing loss by selectively inactivating a dominant mutation in TMC1.

Abstract: The invention relates to compositions and methods for modulating the expression of alpha-ENaC, and more particularly to the downregulation of alpha-ENaC expression by chemically modified oligonucleotides.

Abstract: Genetically modified microorganisms that have the ability to convert carbon substrates into chemical products such as 2,3-BDO; 1,4-BDO; isobutyraldehyde; isobutanol; 1-butanol; n-butanol; ethanol; fatty alcohols; and fatty acid methyl ester are disclosed. For example, genetically modified methanotrophs that are capable of generating 2,3-BDO; 1,4-BDO; isobutyraldehyde; isobutanol; 1-butanol; n-butanol; ethanol; fatty alcohols; and fatty acid methyl ester at high titers from a methane source are disclosed. Methods of making these genetically modified microorganisms and methods of using them are also disclosed. These microorganisms and methods make use of molecular switches to regulate gene expression.

Abstract: A method for extracting protein without lysing cells includes: step 1: combining a penetrating peptide CPP gene having a sequence as set forth in SEQ ID NO: 1 and a bacterial lyase T4L gene having a sequence as set forth in SEQ ID NO: 2 through a flexible connecting peptide GGGGS gene having a sequence as set forth in SEQ ID NO: 3 to form a fusion enzyme CPP-T4L gene having a sequence as set forth in SEQ ID NO: 4; step 2: inserting the fusion enzyme CPP-T4L gene, and obtaining a recombinant host strain; step 3: cloning a target protein expression gene, and then constructing a recombinant expression strain; step 4: first inducing the expression of the target protein expression gene; starting the expression of the fusion enzyme CPP-T4L gene, and releasing a target protein; step 5: collecting cell lysis supernatant to recover the target protein.

Abstract: The present disclosure provides instruments, modules and methods for improved detection of edited cells following nucleic acid-guided nuclease genome editing. The disclosure provides improved automated instruments that perform methods—including high throughput methods—for screening cells that have been subjected to editing and identifying cells that have been properly edited.

Abstract: A gene knock-in method for knocking in an exogenous DNA into a target site of a genomic DNA, the method comprising: a step of introducing a donor DNA that contains the exogenous DNA and a CRISPR-Cas9 system that includes a Cas9 protein and a guide RNA for the Cas9 protein as constituent elements into a cell, wherein the donor DNA contains in order from a 5? side: a 5?-microhomology region formed of a first? nucleotide sequence that is capable of being joined to a first nucleotide sequence on a 5? side of the target site of the genomic DNA by microhomology-mediated end joining; the exogenous DNA; and a 3?-microhomology region formed of a second? nucleotide sequence that is capable of being joined to a second nucleotide sequence on a 3? side of the target site of the genomic DNA by microhomology-mediated end joining, the CRISPR-Cas9 system cleaves, in the genomic DNA, a first cleavage target region between the target site and the first nucleotide sequence and a second cleavage target region between the targ

Abstract: The present disclosure provides a series of mutant Agrobacterium strains generated by random mutagenesis of a wide-type or ? mutant VirD2 gene or VirD2 protein. The mutant Agrobacterium strains of the present disclosure transiently express T-DNA-encoded transgenes in a target plant but do not stably integrate these genes into the plant genome.

Abstract: This document relates to methods and materials for genome engineering in eukaryotic cells, and particularly to methods for increasing genome engineering (i.e. transformation or genome editing) efficiency via delivery of one or more RKD2 and RKD4 genes, with genome engineering components.

Abstract: Compositions and methods and for enhancing the resistance of wheat plants to wheat stem rust caused by Puccinia graminis f sp. tritici are provided. The compositions comprise nucleic acid molecules encoding resistance (R) gene products and variants thereof and plants, seeds, and plant cells comprising such nucleic acid molecules. The methods for enhancing the resistance of a wheat plant to wheat stem rust comprise introducing a nucleic acid molecule encoding an R gene product into a wheat plant cell. Additionally provided are methods for using the wheat plants in agriculture to limit wheat stem rust.

Abstract: A method for creating a new germplasm of a male sterile crop by gene editing and an application thereof are provided. In this method, the gene editing is performed on an exon region of a Ty-5 gene, and a deletion of DNA sequence is introduced by using a repair mechanism of plants themselves to double-strand breaks (DSBs), causing a loss of function of Ty-5 gene, thereby obtaining a male-sterile character. The method can be applied without being limited by crop categories. After the gene editing is performed on Ty-5 genes of various crops, new germplasms can be quickly obtained. The new germplasms have the same agronomic characters as the previous materials, and only differ in sexual aspect, which effectively solves the problem of the lack of male sterile materials and unstable fertility in natural resources.

Abstract: The disclosure in the specification relates to an artificial recombinant chromosome and the use thereof, and more particularly to an artificial recombinant chromosome generated by the recombination of two or more chromosomes and a production of a transgenic animal using a cell including the same. Especially, in the disclosure in the specification, an interchromosomal exchange between the recipient chromosome and the donor chromosome has many merits to produce the artificial recombinant chromosome for producing the transgenic animal.

Abstract: Disclosed herein are methods for producing virus-infected cell lines or animal models, wherein an enveloped virus including a lipid bilayer is mixed with a bile acid or a bile acid derivative, which allows the lipid bilayer to be replaced with a lipid bilayer derived from a target animal. Also disclosed herein are the virus-infected cell lines or animal models so produced and methods of screening a therapeutic candidate for a viral disease using the same.

Abstract: An adeno-associated virus (AAV) vector for inserting a desired nucleic acid into a nucleic acid in a cell, wherein the nucleic acid in the cell comprises a region consisting of a first nucleotide sequence and a region consisting of a second nucleotide sequence in order in a direction from a 5? end to a 3? end, wherein the vector comprises a first gRNA target sequence, a region consisting of a first nucleotide sequence, the desired nucleic acid, a region consisting of a second nucleotide sequence, a second gRNA target sequence, a cell-specific promoter, a sequence encoding a Cas9 nuclease, an RNA polymerase III promoter, a sequence encoding a first gRNA recognizing the first gRNA target sequence and a sequence encoding a second gRNA recognizing the second gRNA target sequence, wherein the vector yields a nucleic acid fragment comprising a region consisting of a first nucleotide sequence, the desired nucleic acid and the region consisting of the second nucleotide sequence by the Cas9 nuclease, wherein a first n

Abstract: Provided herein are methods and compositions for plakophilin-2 gene therapy for treating heart diseases such as arrhythmogenic right ventricular cardiomyopathy (ARVC) or arrhythmogenic cardiomyopathy (ACM).

Abstract: The application relates to MSBI (Multiple Sclerosis Brain Isolate) nucleotide sequences as well as probes and primers comprising part of said nucleotide sequences and antibodies against polypeptides encoded by said nucleotide sequences. These compounds are useful as early markers for the future development of cancer and diseases of the CNS (Multiple sclerosis MS, Prion-linked diseases, amyotrophic lateral sclerosis, transmissible spongiforme encephalitis, Parkinson's disease, Alzheimer disease) and should represent targets for treatment and prevention.

Abstract: In some aspects, promoters, vectors, and methods of selectively inducing expression in subtypes of neuronal cells are provided. In some embodiments, single promoters can be used to restrict access to sub-populations of neurons. In some embodiments, single promoters active in different sub-populations of neurons can be used together to access a larger sub-population of neurons than either promoter alone (“set summation”).

Abstract: Provided herein are expression cassettes for expressing a transgene in a liver cell, wherein the transgene encodes a PAH polypeptide. Also provided are methods to treat phenylketonuria (PKU) and/or to reduce levels of phenylalanine in an individual in need thereof. Further provided herein are vectors (e.g., rAAV vectors), viral particles, pharmaceutical compositions and kits for expressing a PAH polypeptide in an individual in need thereof.

Abstract: The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

Abstract: The present invention refers to a method to convert H2 and CO2 into methane by methanogenic microorganisms in a bioreactor in a continuous production process for methane enriched gas compositions, while culturing the methanogenic microorganisms under cell retention conditions and continuously removing metabolic water in the cell culture medium.

Abstract: An engineered microbial cell expressing a ?-amyrin synthase, a cytochrome P450 reductase, a cytochrome P450 C28 oxidase, a cytochrome P450 C16 oxidase and a cytochrome C23 oxidase is used to make quillaic acid from ?-amyrin.

Abstract: This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.

Abstract: The present invention relates to the production of vanillin via the bioconversion of isoeugenol. The bioconversion can be mediated in a cellular system (e.g., an Escherichia coli bacterium), or in an enzymatic reaction mixture without a cellular system.

Abstract: The present invention relates to the production of vanillin via the bioconversion of isoeugenol. The bioconversion can be mediated in a cellular system (e.g., an Escherichia coli bacterium), or in an enzymatic reaction mixture without a cellular system.

Abstract: A method for biologically producing acetin such as monoacetin, diacetin, or triacetin according to an embodiment of the present disclosure includes reacting acetyl-CoA with glycerol in the presence of a first O-acetyl transferase to obtain the acetin. With the method, acetin which is sustainable and safe, and has more excellent quality while not causing environmental pollution may be obtained.

Abstract: The present invention relates to a recombinant microbial host cell comprising an operative biosynthetic metabolic pathway capable of producing one or more compounds selected from the group consisting of L-dopa, dopamine, (S)-Norcoclaurine and derivatives thereof; said pathway comprising a heterologous L-tyrosine hydroxylase (TyrH) converting L-Tyrosine into L-dopa capable of increasing the cell production of the Compound compared to a reference L-tyrosine hydroxylase having the sequence set forth in SEQ ID NO: 58.

Abstract: A method for producing L-lysine by fermentation, comprising modifying a gene for coding an NCBI reference sequence NP_601029.1 and/or NP_599350.1 on a Corynebacterium bacterial chromosome to enable the activity and/or expression quantity of NP_601029.1 and/or NP_599350.1 to be reduced; replacing a promoter of one or more genes on the Corynebacterium bacterial chromosome with a EP5 promoter, and fermenting bacteria obtained by modification to produce L-lysine. Also provided are methods and applications derived from the method, and bacteria and promoter that can used in the methods and the applications.

Abstract: The present invention discloses a kind of method for preparing L-citrulline by using Aeromonas sp., which is related to the technical field of bioengineering. The said method consists of following steps: fermenting Aeromonas sp. in a culture medium to obtain seed liquid, and the liquid is inoculated into the fermenter at an inoculum size of 1-2% by volume. The initial pH is 3.5, and the pH in the medium is controlled below 4.0 all the time. Then, conducts shaking culture for 15-20 hours to obtain the fermentation broth. The fermentation broth is centrifuged to obtain precipitation solution and supernatant; Use the said supernatant to prepare the substrate solution, and the pH of the substrate solution is controlled at 3-5, and then, add the precipitation solution to react at the temperature of 30-50° C., the reaction time is 5-8 hours. After reaction, the L-citrulline is obtained by the method of concentration and crystallization.

Abstract: The present invention provides for a genetically modified fungal host cell capable of producing indigoidine, wherein the host cell comprises a non-ribosomal peptide synthetase (NRPS) that converts glutamine to indigoidine.

Abstract: Described is a method for the production of fructose-6-phosphate (F6P) from dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P) comprising the steps of: (a) enzymatically converting dihydroxyacetone phosphate (DHAP) into dihydroxyacetone (DHA); and (b) enzymatically converting the thus produced dihydroxyacetone (DHA) and glyceraldehyde-3-phosphate (G3P) into fructose-6-phosphate (F6P); or comprising the steps of: (a?) enzymatically converting glyceraldehyde-3-phosphate (G3P) into glyceraldehyde; and (b?) enzymatically converting the thus produced glyceraldehyde together with dihydroxyacetone phosphate (DHAP) into fructose-1-phosphate (F1P); and (c?) enzymatically converting the thus produced fructose-1-phosphate (F1P) into fructose-6-phosphate (F6P).

Abstract: Provided is a method for improving the production amount of a tri- or higher galactooligosaccharide and the reaction rate by a method for producing a galactooligosaccharide characterized by allowing ?-galactosidase to react with a substrate in the presence of 5 to 60 mM sodium ions and 0.5 to 8 mM magnesium ions.

Abstract: The invention relates to the use of specific terminal deoxynucleotidyl transferase (TdT) enzymes in a method of nucleic acid synthesis, to methods of synthesizing nucleic acids, and to the use of kits comprising said enzymes in a method of nucleic acid synthesis. The invention also relates to the use of terminal deoxynucleotidyl transferases and 3?-blocked nucleotide triphosphates in a method of template independent nucleic acid synthesis.

Abstract: The present disclosure provides genetically modified insect cells that can produce glycosylated expression products having a human-like glycosylation pattern. In particular, the cells comprise disruption of the fdl and/or FucT6 genes. Also provided is expression systems and methods for recombinant protein production.