Abstract: Methods of uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are also provided. The molecules to be labeled may include, but are not limited to, RNAs and/or cDNAs.

Abstract: The present invention relates to a method of using a receptor (e.g., chimeric antigen receptor—CAR) that activates an immune response upon binding a cancer cell ligand in conjunction with a target-binding molecule that targets a protein or molecule for removal or neutralization to generate enhanced anti-cancer immune cells. The present invention also relates to engineered immune cells having enhanced therapeutic efficacy and uses thereof.

Abstract: Disclosed herein are methods of determining the sequence and/or positions of modified bases in a nucleic acid sample present in a circular molecule with a nucleic acid insert of known sequence comprising obtaining sequence data of at least two insert-sample units. In some embodiments, the methods comprise obtaining sequence data using circular pair-locked molecules. In some embodiments, the methods comprise calculating scores of sequences of the nucleic acid inserts by comparing the sequences to the known sequence of the nucleic acid insert, and accepting or rejecting repeats of the sequence of the nucleic acid sample according to the scores of one or both of the sequences of the inserts immediately upstream or downstream of the repeats of the sequence of the nucleic acid sample.

Abstract: Hot melt extrusion is disclosed as a process for forming vaginal drug delivery films. The methods involve extruding a composition comprising one or more active pharmaceutical ingredients and one or more polymer carriers at an elevated temperature through a die to thereby provide the film. Films prepared by hot melt extrusion are also described.

Abstract: Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human VH gene segment, a plurality of human DH gene segments and a plurality of human JH gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.

Abstract: The present invention provides a modified RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand targets an HBV mRNA; all of the nucleotide sugars of the RNAi agent are 2?-modified; and at least one of the sense and antisense strands is conjugated to at least one targeting ligand that comprises two or more building blocks connected to a biantennary or triantennary branched linker, optionally via one or more linking groups.

Abstract: Next Generation DNA sequencing promises to revolutionize clinical medicine and basic research. However, while this technology has the capacity to generate hundreds of billions of nucleotides of DNA sequence in a single experiment, the error rate of approximately 1% results in hundreds of millions of sequencing mistakes. These scattered errors can be tolerated in some applications but become extremely problematic when “deep sequencing” genetically heterogeneous mixtures, such as tumors or mixed microbial populations. To overcome limitations in sequencing accuracy, a method Duplex Consensus Sequencing (DCS) is provided. This approach greatly reduces errors by independently tagging and sequencing each of the two strands of a DNA duplex. As the two strands are complementary, true mutations are found at the same position in both strands. In contrast, PCR or sequencing errors will result in errors in only one strand.

Abstract: This disclosure relates to oligonucleotides, compositions and methods useful for reducing ALDH2 expression, particularly in hepatocytes. Disclosed oligonucleotides for the reduction of ALDH2 expression may be double-stranded or single-stranded, and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of ALDH2 expression may also include targeting ligands to target a particular cell or organ, such as the hepatocytes of the liver, and may be used to treat alcoholism and related conditions.

Abstract: Provided are methods for increasing the amount or activity of FMR1 RNA, and in certain instances of increasing the amount of FMRP protein, in an animal Such methods are useful to prevent or ameliorate at least one symptom of a Fragile X-Spectrum disorder. Such Fragile X-Spectrum disorders include FXS, FXTAS, and FXPOI.

Abstract: Methods are provided for detecting a single compound analyte immobilized to a solid substrate by serially contacting and removing different probes to the same analyte.

Abstract: Disclosed herein are methods and compositions for inactivating CCR-5 genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs, such as adenovirus (Ad) vectors, and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.

Abstract: Described herein are systems and methods for treating, inhibiting, or ameliorating X-linked disorders including Wiskott-Aldrich Syndrome (WAS) and X-linked thrombocytopenia (XLT) in subjects that have been identified or selected as being ones that would benefit from a therapy to treat, inhibit, or ameliorate WAS or XLT. The systems include nuclease and vector donor constructs configured for co-delivery to modify endogenous WAS locus.

Abstract: A system for DNA gene assembly that utilizes a DNA symbol library and a DNA linker library. The symbol library has a number of DNA symbols each having a first overhanging end and a second overhanging end different than and non-complimentary to the first end, the first and second ends being the same nucleotides for each DNA symbol. The linker library has pairs of DNA linkers, a first linker of a pair having a first end and a second end and a second linker of the pair having a first end and a second end, the first end of the first linker being the same nucleotides for each first linker and the second end of the second linker being the same nucleotides for each second linker, wherein the second end of the first linker and the first end of the second linker have complementary nucleotides. The first linker joins to the first end of a DNA symbol and the second linker joins to the second end of another DNA symbol.

Abstract: Disclosed are polynucleotides, compositions, and methods related to RNA interference (RNAi). The disclosed polynucleotides, compositions, and methods may be utilized for treating diseases and disorders through RNAi. Particular disclosed are toxic RNAi active seed sequences and methods of using toxic RNAi active sequences for killing cancer cells. The disclosed toxic RNAi active seed sequences preferentially target and inhibit the expression of multiple essential genes for cell survival and/or growth through a process called “death-induced by survival gene elimination” or “DISE.

Abstract: Provided herein are RNAi molecules for treating Huntington's disease. Further provided herein are expression cassettes, vectors (e.g., rAAV, recombinant adenoviral, recombinant lentiviral, and recombinant HSV vectors), cells, viral particles, and pharmaceutical compositions containing the RNAi. Yet further provided herein are methods and kits related to the use of the RNAi, for example, to treat Huntington's disease.

Abstract: Provided are promoters and a method of producing L-amino acid using the same.

Abstract: A ?-modified phosphoric acid compound precursor that inhibits the progress of a phosphorylation reaction having a partial structure represented by where A1 represents —SR1, —S—S—R1, —SeR1, or —X, where X is a halogen selected from fluoro, chloro, bromo, and iodo; R1 represents hydrogen, an alkyl group having 1 to 20 carbon atoms, or the like; L1 represents hydrogen, an alkyl group having 1 to 20 carbon atoms, or the like; L2 represents an alkyl group having 1 to 20 carbon atoms, or the like; L1 and L2 may be linked to each other to form a 4 to 6-membered ring structure; L1 and L2 may each have a substituent; and the symbol * represents a bond to be bonded to a phosphate group by phosphorylation. Further, provided are a reaction inhibitor and a medicine, each of which includes the ?-modified phosphoric acid compound precursor.

Abstract: The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.

Abstract: The present disclosure provides a novel integrated entropy-based method that combines genome-wide profiling and network analyses for diagnostic and prognostic applications. The present disclosure further provides the integration of multiomics datasets, network analyses and machine learning that enable predictions on diagnosing infectious diseases and predicting the probability that they will escape treatment/the host immune system and/or become antibiotic resistant. The present disclosure provides a primary gateway towards the development of highly accurate infectious disease prognostics.

Abstract: The present disclosure provides materials and methods for the delivery of therapeutic nucleic cells (and imaging agents) to tissues.

Abstract: Embodiments of the present invention provide plant-derived extracts as a replacement for traditional cryoprotectants used to freeze tissue and cells providing a method to decrease post-thaw damage as created by the cryoprotectant. For example, extracts from the genus Hippophae or other plant sources or compositions may be used as a cryoprotectant or may even be used to replace at least some of a traditional cryoprotectant.

Abstract: Next Generation DNA sequencing promises to revolutionize clinical medicine and basic research. However, while this technology has the capacity to generate hundreds of billions of nucleotides of DNA sequence in a single experiment, the error rate of approximately 1% results in hundreds of millions of sequencing mistakes. These scattered errors can be tolerated in some applications but become extremely problematic when “deep sequencing” genetically heterogeneous mixtures, such as tumors or mixed microbial populations. To overcome limitations in sequencing accuracy, a method Duplex Consensus Sequencing (DCS) is provided. This approach greatly reduces errors by independently tagging and sequencing each of the two strands of a DNA duplex. As the two strands are complementary, true mutations are found at the same position in both strands. In contrast, PCR or sequencing errors will result in errors in only one strand.

Abstract: The invention relates to a method for the detection of the occurrence of initiation of replication events in genomic DNA in a eukaryotic cell, involving contacting said eukaryotic cell comprising said genomic DNA with a first nucleotide probe, under conditions enabling in situ hybridization of said first nucleotide probe with a target region in the DNA genome, wherein said target region comprises a nucleic acid sequence which has no identified corresponding annealing RNA in a metabolically active cell and therefore remains RNA-free during transcription and replication of said DNA genome and detecting said first nucleotide probe hybridized to said DNA. Further detection of at least one RNA molecule can be achieved.

Abstract: Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human VH gene segment, a plurality of human DH gene segments and a plurality of human JH gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.

Abstract: The disclosed method rapidly identifies with desired accuracy AML patients, including elderly AML patients, likely to respond to treatment with a combination of a farnesyltransferase inhibitor and one or more of etoposide, teniposide, tamoxifen, sorafenib, paclitaxel, temozolomide, topotecan, trastuzumab and cisplatinum. In an embodiment, the improvements include the use of whole blood rather than the customary bone marrow sample, thus making the assay more accurate, rapid, less intrusive, less expensive as well as less painful. The method includes evaluation of a two-gene expression ratio (RASGRP1:APTX), which with a corresponding threshold, provides sufficient accuracy for predicting the response to the combination treatment. In the preferred embodiment the combination treatment combines tipifarnib (R115777, ZARNESTRA®) with etoposide.

Abstract: This invention relates to methods and compositions for coupling nucleic acid to a functionalized surface or support. In particular, the present invention provides an improved process for coupling aminated nucleic acid to a support functionalized with carboxylic acid groups, wherein the coupling reaction is conducted in the presence of an organic solvent. The invention further relates to compositions and kits for performing the coupling reaction and uses of nucleic acid-loaded supports for various applications.

Abstract: The present invention relates to methods for treating and/or preventing tumors and/or promoting apoptosis in a neoplastic cell comprising contacting the neoplastic cell with an cell-penetrating dominant-negative ATF5 (“CP-d/n-ATF5”), wherein the CP-d/n-ATF5 is capable of inhibiting ATF5 function and/or activity.

Abstract: Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the PI3K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the PI3K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.

Abstract: The present disclosure provides novel bacterial strains with altered expression or start codon modification of one or more RNA degradation/processing genes. The RNA degradation genes of the present disclosure are controlled by heterologous promoters. The present disclosure further describes methods for generating microbial strains comprising heterologous promoter sequences operably linked to RNA degradation/processing genes.

Abstract: Described herein are methods and compositions for genomic editing. Endonucleases for genomic editing involve inducing breaks in double stranded DNA, for which knock-ins are notoriously inefficient for relying on random integration of homologous DNA sequences into the break site by repair proteins. To address these issues, described herein are novel recombinant fusion proteins that actively recruit linear DNA inserts in closer proximity to the genomic cleavage site, increasing integration efficiency of large DNA fragments into the genome. Such improvements to genomic editing technology allow one to use lower linear DNA concentrations without sacrificing efficiency and can be further combined with other features, such as fluorescent protein reporting systems.

Abstract: This invention provides a kit or device for detection of prostate cancer and a method for detecting prostate cancer. This invention provides a kit or device for detection of prostate cancer comprising a nucleic acid capable of specifically binding to an miRNA in a sample from a subject or a complementary strand thereof and a method for detecting prostate cancer comprising measuring the miRNA in vitro.

Abstract: According to an aspect, provided are: a guide RNA; a vector comprising the same; a composition for removing a nucleic acid sequence encoding a KRAS polypeptide in the genome of a cell, containing the same; a composition for preventing or treating cancer, containing the same; and a method using the same. The present invention enables the mutation of a nucleic acid sequence encoding a KRAS polypeptide in the genome of a cell or a subject and, particularly, can be usable, as personalized or precision medical care, in the prevention or treatment of cancer.

Abstract: Compositions, systems, and methods for the display of analytes such as biomolecules are described. Display of analytes is achieved by coupling of the analytes to displaying molecules that are configured to associate with surfaces or interfaces. Arrays of analytes may be formed from the described systems for utilization in assays and other methods.

Abstract: The subject invention relates in part to the surprising discovery that Cry1Da is active against corn earworm (CEW), Helicoverpa zea (Boddie). Methods for using Cry1Da in transgenic plants to prevent serious crop damage is described. Leaf and silk bioassays using transgenic maize expressing full length, core toxin region or chimeric Cry1Da demonstrated good insect protection against CEW larvae damage.

Abstract: Improved compositions and methods for treating a disease or disorder through target exon skipping, and preferably muscular dystrophy by administering antisense thiomorpholino molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping to produce a functional Dystrophin protein.

Abstract: This application provides methods, kits, probes and primers, that can be used to analyze environmental samples, such as water samples, soil samples, and air samples. The methods and kits can include positive controls, to provide confidence in test results.

Abstract: The present invention relates to a method for single-cell imaging mass spectrometry (MS) by correlating an optical image of a cell sample with an MS image. The method of the invention is in particular useful in research to test concomitantly optical and molecular phenotypes at a single-cell resolution.

Abstract: The present invention relates to novel nucleic acid molecules, called aptamers, that bind specifically to a small molecule fluorophore and thereby enhance the fluorescence signal of the fluorophore upon exposure to radiation of suitable wavelength. Molecular complexes formed between the novel fluorophores, novel nucleic acid molecules, and their target molecules are described, and the use of multivalent aptamer constructs as fluorescent sensors for target molecules of interest are also described.

Abstract: Provided are compositions comprising an oligonucleotide that targets Thymic stromal lymphopoietin (TSLP). The oligonucleotide may include a small interfering RNA (siRNA) or an antisense oligonucleotide (ASO). Also provided herein are methods of treating an airway disorder by providing an oligonucleotide that targets TSLP to a subject in need thereof. In some embodiments, the oligonucleotide targeting is specific for a long isoform of TSLP (1fTSLP).

Abstract: Sensing the electric or strain field experienced by a sample containing a crystal host comprising of solid state defects under a zero-bias magnetic field can yield a very sensitive measurement. Sensing is based on the spin states of the solid-state defects. Upon absorption of suitable microwave (and optical) radiation, the solid-state defects emit fluorescence associated with hyperfine transitions. The fluorescence is sensitive to electric and/or strain fields and is used to determine the magnitude and/or direction of the field of interest. The present apparatus is configured to control and modulate the assembly of individual components to maintain a zero-bias magnetic field, generate an Optically Detected Magnetic Resonance (ODMR) spectrum (with or without optical excitation) using appropriate microwave radiation, detect signals based on the hyperfine state transitions that are sensitive to electric/strain fields, and to quantify the magnitude and direction of the field of interest.

Abstract: Provided herein are compositions and systems for use in polymerase-dependent, nucleotide transient-binding methods. The methods are useful for deducing the sequence of a template nucleic acid molecule and single nucleotide polymorphism (SNP) analyses. The methods rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide. The labeled nucleotides transiently-binds the polymerase in a template-dependent manner, but does not incorporate. The methods are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation.

Abstract: A vaccine composition for immunizing and/or protecting a mammal against an IL-31 mediated disorder is provided, wherein the composition includes: the combination of a carrier polypeptide and at least one mimotope selected from a feline IL-31 mimotope, a canine IL-31 mimotope, a horse IL-31 mimotope, and a human IL-31 mimotope; and an adjuvant. Such vaccines can be in the form of pharmaceutical compositions useful for treating or protecting mammals such as cats, dogs, horses, or humans against IL-31-mediated disorders.

Abstract: The invention described in the application relates to a panel of gene expression markers for patient with a tumor. The invention thus provides methods and compositions, e.g., kits, for evaluating gene expression levels of the markers and methods of using such gene expression levels to evaluate the likelihood of disease progression or response to chemotherapy or radiation therapy. Such information can be used in determining prognosis and treatment options for cancer patients.

Abstract: Disclosed are dendritic anionic lipids which are compounds of Formula (I): wherein R and R1 are non-polar groups, L is a linking moiety, and Dm is a dendritic moiety of m generations, each as defined herein. These dendritic anionic lipids are useful for delivery and expression of m RNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

Abstract: A ribonucleic acid compound is disclosed, the ribonucleic acid compound comprising, or consisting of, an RNA sequence having at least 90% sequence identity to SEQ ID NO: 1, wherein said RNA sequence has a length of 29 nucleotides or fewer, and wherein the RNA sequence is capable of binding to a transferrin receptor (TfR).

Abstract: Disclosed herein include systems, methods, compositions, and kits for in situ readout of barcodes, such as DNA barcodes. Barcode constructs containing a promoter (e.g., a phage promoter) that is inactive in live cells can be integrated in the genomes of cells. Cells can be fixed, and phage RNA polymerase can be used for transcription of the barcode to RNA transcripts. The RNA transcripts can be detected using, for example, fluorescent imaging and used to determine barcode sequences.

Abstract: The present disclosure relates to methods, processes and systems for enzymatic synthesis of oligonucleotide from a single-stranded, immobilized primer in the presence of a polymerase. Using the disclosed methods single-stranded oligonucleotides can be synthesized enzymatically from a single-stranded, immobilized primer in the presence of deoxyribonucleotide triphosphates or ribonucleotide triphosphates. Dideoxyribonucleotide triphosphates, deoxyribonucleotide triphosphates with reversible terminators, or ribonucleotide triphosphates with reversible terminators can be added enzymatically to the end of the primer or its extension products. According to the disclosed method, a single-stranded primer can bind to a template such that the thus-formed double-stranded structure can allow the polymerase to extend the primer at 3? end.

Abstract: The present invention relates to a highly efficient aptamer complex comprising a branched DNA and an aptamer, and a pharmaceutical use thereof. More specifically, the aptamer complex of the present invention relates to a highly efficient aptamer complex including a Y-shaped DNA as the branched DNA and using vascular endothelial growth factor (VEGF) as a target molecule. The aptamer complex of the present invention and a pharmaceutical composition comprising the same as an active ingredient are expected to be widely used in the medical field since the binding efficiency with the target molecule is more remarkable than that of the conventional aptamer.

Abstract: The invention generally relates to compositions for maximizing capture of affinity-labeled molecules on solid supports. The disclosed methods and compositions were developed to maximize depletion of ribosomal RNA from total RNA samples, which is useful to improve the quality of RNA preparations used for applications such as massively parallel sequencing. The RNA depletion method is based on using long affinity-labeled RNA molecules that are complementary to all or part of the target ribosomal RNAs, as subtractive hybridization probes.

Abstract: Engineered Cry1Da amino acid sequences are provided that exhibit improved Lepidopteran insecticidal activity and an enhanced Lepidopteran spectrum compared to the naturally occurring Cry1Da protein toxin. Polynucleotide sequences intended for use in expression of the improved proteins in plants are also provided. Particular embodiments provide compositions containing insect inhibitory amounts of the engineered proteins, as well as recombinant plants, plant parts, and seeds containing polynucleotide constructs encoding one or more of the improved engineered proteins.