Abstract: Methods of treating cancer or enhancing sensitivity to cancer therapies, including immunotherapies by increasing tumor mutation burden, are provided. The methods use therapeutics directed against DNA polymerase proofreading and/or mismatch repair enzymes such as MLH1, MSH2, MSH6 or PMS2. The therapeutics can be used alone, in tandem or in combination with other cancer therapies, in particular with immunotherapies. Also provided are antisense therapeutics targeting DNA polymerase proofreading and/or mismatch repair enzymes.

Abstract: Aspects of the disclosure includes methods for preparing an amorphous solid composition of a fatty acid metal salt. In practicing the subject methods according to certain embodiments, a succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane organic salt is contacted with a metal base to produce a succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane metal salt; and the succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane metal salt is precipitated in a solvent to produce an amorphous solid succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane metal salt composition. An amorphous solid succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane lithium salt is also provided.

Abstract: A genetically modified fruit-producing plant, said plant having sufficiently reduced total Polyphenol Oxidase (PPO) activity relative to a wild type of said plant to reduce browning in the fruit of said plant relative to said wild type, wherein the reduced total PPO activity results from a reduction in activity of at least two PPO isoenzymes in said plant relative to said wild type, or a cell, seed, seedling, part, tissue, cell, fruit or progeny of said plant.

Abstract: The present invention discloses a sequencing library comprising a nucleotide sequence. The sequence comprises a linker sequence and two target sequences. Two ends of the linker sequence are respectively linked to the target sequences and the two target sequences are direct repeat sequences. The present invention further discloses preparation and use of the sequencing library. The present invention overcomes the high error rate problem of current DNA sequencing technologies, especially in a way of very low coverage bias, and can be used to detect low frequency mutations in different kinds of samples.

Abstract: The present invention relates to a method of functionalization of at least one ribonucleic acid (RNA) molecule, contained in a liquid sample, which includes the following steps: a) providing at least: one binding molecule consisting of an aza-isatoic anhydride or a derivative thereof, one group of interest, and one linkage joining the binding molecule to the group of interest, b) reacting the anhydride function of the binding molecule with at least one hydroxyl group carried: in position 2? of the ribose of one of the RNA nucleotides, and/or in position(s) 2? and/or 3? of the ribose of the nucleotide at the terminal 3? end of the RNA, and obtaining an aza-anthranilate that joins, by means of the linkage, the RNA to the group of interest.

Abstract: The present disclosure relates, in some embodiments, to compositions, organisms, systems, and methods for expressing a gene product in a plant using a expression control sequence (ECS) operable in monocots and/or dicots. For example, (i) an isolated nucleic acid may comprise an ECS (e.g., a sugarcane bacilliform virus promoter) and, optionally, an exogenous nucleic acid (ExNA) operably linked to the ECS; (ii) an expression vector may comprise an ECS; an ExNA; and, optionally, a 3? termination sequence, wherein the ECS has promoter activity sufficient to express the ExNA in at least one monocot and at least one dicot; (iii) a microorganism, plant cell, or plant may comprise an isolated nucleic acid; (iv) a method for constitutively expressing an ExNA in a plant (e.g.

Abstract: An analyte is separated from a fluid sample by introducing the sample into a cartridge having a sample port and a first flow path extending from the sample port. The first flow path includes an extraction chamber containing a solid support for capturing the analyte from the sample. The cartridge has a second flow path for eluting the captured analyte from the extraction chamber, the second flow diverging from the first flow path after passing through the extraction chamber. The sample is forced to flow through the extraction chamber and into a waste chamber, thereby capturing the analyte with the solid support as the sample flows through the extraction chamber. The captured analyte is then eluted from the extraction chamber by forcing an elution fluid to flow through the extraction chamber and along the second flow path.

Abstract: Nucleic acid labeling compounds are disclosed. The compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Abstract: This application relates to iRNA agents and methods of making and using the agents. The iRNA agent comprises a sense sequence and an antisense sequence. The antisense strand and/or the sense strand may contain formula (8) or its L-nucleoside or 2?-5? linkage isomer: The iRNA agents of the invention can present increased nuclease resistance.

Abstract: An analyte is separated from a fluid sample by introducing the sample into a cartridge having a sample port and a first flow path extending from the sample port. The first flow path includes an extraction chamber containing a solid support for capturing the analyte from the sample. The cartridge has a second flow path for eluting the captured analyte from the extraction chamber, the second flow diverging from the first flow path after passing through the extraction chamber. The sample is forced to flow through the extraction chamber and into a waste chamber, thereby capturing the analyte with the solid support as the sample flows through the extraction chamber. The captured analyte is then eluted from the extraction chamber by forcing an elution fluid to flow through the extraction chamber and along the second flow path.

Abstract: The present invention relates to transgenic Ficus plants, particularly Ficus carica (fig tree), to a method for producing same, and to Ficus plants, plant materials and plant products produced by or from such genetically modified plant material. More specifically, the present invention relates to transgenic Ficus carica plants and use thereof for producing trees having improved agricultural traits and for the production of foreign proteins and edible vaccines.

Abstract: Processes are disclosed that use 3?-reversibly terminated nucleoside triphosphates to analyze DNA for purposes other than sequencing using cyclic reversible termination. These processes are based on the unexpected ability of terminal transferase to accept these triphosphates as substrates, the unexpected ability of polymerases to add reversibly and irreversibly terminated triphosphates in competition with each other, the development of cleavage conditions to remove the terminating group rapidly, in high yield, and without substantial damage to the terminated oligonucleotide product, and the ability of reversibly terminated primer extension products to capture groups. The presently preferred embodiments of the disclosed processes use a triphosphate having its 3?-OH group blocked as a 3?-ONH2 group, which can be removed in buffered NaNO2 and use variants of Taq DNA polymerase, including one that has a replacement (L616A).

Abstract: The present invention provides modified oligomeric compounds and compositions of oligomeric compounds for use in the RNA interference pathway of gene modulation. The modified oligomeric compounds include siRNA and asRNA having at least one affinity modification.

Abstract: The invention relates to the therapeutic use of novel stabilized oligoribonucleotides as immune modulatory agents for immune therapy applications. Specifically, the invention provides novel RNA-based oligoribonucleotides with improved nuclease and RNase stability and that selectively induce immune modulatory activity through TLR7.

Abstract: A group I intron-derived ribozyme which binds RNA in trans, excises an internal segment from within the RNA, and splices the remaining 5? and 3? ends of the RNA back together (the trans-excision-splicing reaction) is disclosed. The excised segment can be as long as 28 nucleotides, or more, and as little as one nucleotide. The ribozymes of the invention are easily modified to alter their sequence specificity. Such ribozymes represent a new and potentially powerful class of generally adaptable genetic therapeutics.

Abstract: Oligomeric compounds including oligoribonucleotides and oligoribonucleosides are provided that have subsequences of 2?-pentoribofuranosyl nucleosides that activate dsRNase. The oligoribonucleotides and oligoribonucleosides can include substituent groups for increasing binding affinity to complementary nucleic acid strand as well as substituent groups for increasing nuclease resistance. The oligomeric compounds are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics. Also included in the invention are mammalian ribonucleases, i.e., enzymes that degrade RNA, and substrates for such ribonucleases. Such a ribonuclease is referred to herein as a dsRNase, wherein “ds” indicates the RNase's specificity for certain double-stranded RNA substrates.

Abstract: The present invention concerns methods for controlling insect infestation via RNAi-mediated gene silencing, whereby the intact insect cell(s) are contacted with a double-stranded RNA from outside the insect cell(s) and whereby the double-stranded RNA is taken up by the intact insect cell(s). In one particular embodiment, the methods of the invention are used to alleviate plants from insect pests. Alternatively, the methods are used for treating and/or preventing insect infestation on a substrate or a subject in need of such treatment and/or prevention. Suitable insect target genes and fragments thereof, dsRNA constructs, recombinant constructs and compositions are disclosed.

Abstract: The present invention relates to a method and compounds for hydrolysing nucleic acids. In particular it relates to compounds that can be used for the preferential cleavage of a phosphodiester bond at a specific position in RNA.

Abstract: Nucleic acid labeling compounds are disclosed having the formula: These compounds are useful for attaching a detectable label to a nucleic acid.

Abstract: Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Abstract: The invention relates to modulation of the immune system. More particularly, the invention relates to modulating the immune system through the use of oligonucleotide-derived compounds. The invention provides immunostimulatory agents that are less expensive to make than existing immunostimulatory oligonucleotides. The immunostimulatory agents according to the invention can, in preferred embodiments, cause immune stimulation across species lines.

Abstract: A method for converting a pseudoisocytidine base having the formula: to a pseudoisocytidine molecule having the formula: is disclosed. Such compounds are useful as nucleic acid labeling compounds.

Abstract: Compounds of the following structure: are useful as nucleic labeling compounds.

Abstract: Method for splicing a target nucleic acid molecule with a separate nucleic acid molecule. Such splicing generally causes production of a chimeric protein with advantageous features over that protein naturally produced from the target nucleic acid prior to splicing. The method includes contacting the target nucleic acid molecule with a catalytic nucleic acid molecule including the separate nucleic acid molecule. Such contacting is performed under conditions in which at least a portion of the separate nucleic acid molecule is spliced with at least a portion of the target nucleic acid molecule to form a chimeric nucleic acid molecule. In this method, the catalytic nucleic molecule is chosen so that it is not naturally associated with the separate nucleic acid molecule.

Abstract: Oligonucleotides and other macromolecules are provided which have increased nuclease resistance, substituent groups for increasing binding affinity to complementary strand, and subsequences of 2?-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H. Such oligonucleotides and macromolecules are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to oligonucleotide therapeutics.

Abstract: The invention provides polyamide-oligonucleotide derivatives of the formula: F[(DNA-Li)q(PNA-Li)r(DNA-Li)s(PNA)t]xF?. In the formula, q, r, s, and t are, independently of one another, zero or 1, where the total of two or more adjacent q, r, s, and t is greater than or equal to 2; and x is 1 to 20. In the formula, DNA is a nucleic acid such as DNA or RNA or a known derivative thereof. Li is a covalent linkage between DNA and PNA, where the covalent linkage comprises a bond or an organic radical with at least one atom from the series consisting of C, N, O, or S. PNA is a polyamide structure which contains at least one nucleotide base that is different from thymine. F and F? are end groups and/or are linked together by a covalent bond. The invention also provides physiologically tolerated salts of the above formula. The invention further provides a process for preparation of the polyamide-oligonucleotide derivatives of the invention as well as their use as pharmaceuticals, as gene probes, and as primers.

Abstract: The present invention relates to conjugates of synthetic binding units and nucleic acids. The present invention also relates to methods for sorting and immobilizing nucleic acids on support materials using such conjugates by specific molecular addressing of the nucleic acids mediated by the synthetic binding systems. Particularly, the present invention also relates to novel methods of utilizing conjugates of synthetic binding units and nucleic acids to in active electronic array systems to produce novel array constructs from the conjugates, and the use of such constructs in various nucleic acid assay formats. In addition, the present invention relates to various novel forms of such conjugates, improved methods of making solid phase synthesized conjugates, and improved methods of conjugating pre-synthesized synthetic binding units and nucleic acids.

Abstract: Nucleic acid labeling compounds including the following structure are disclosed: wherein A is a triphosphate group with apporpriate counterions, said counterions selected from the group consisting of H+, Na+, Li+, K+, and NH4+; X is O; Y is OH; Z is OH; L is selected from the group consisting of —CH?CH—C(O)—NH—CH2—CH2—NH—C(O)— and —CH2—CH2—C(O)—NH—CH2—CH2—NH—C(O); M is —(CH2)45—NH—, n is 1 and Q is biotin having the structure: The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Abstract: The use of protection schemes and solid phase synthesis reactions to generate molecules of core structure M, which have a plurality of moieties, each of which can be individually deprotected or subsequently derivatized are provided. In one process, M is a multifunctional low molecular weight compound, such as a saccharide, aminosugar, deoxysugar, nucleoside, nucleotide, coenzyme, amino acid, lipid, steroid, vitamin, hormone, alkaloid, or small molecule drug. In another process, M is an oligomeric compound, such as an oligosaccharide, oligonucleotide, peptide or protein.

Abstract: A compound having the formula: wherein, R1 represents 2′-O-alkylthioalkyl or 2′-C-alkylthioalkyl; X represents a base or H; Y represents a phosphorus-containing group; and R2 represents H, DMT or a phosphorus-containing group.

Abstract: The present invention is a general method for irreversibly inactivating ribonucleases. Ribonucleases are completely inactivated by treating them with a reducing agent and heat. RNA samples contaminated with ribonuclease may be treated with this method to protect them from degradation. The RNA may then be used directly in a variety of enzymatic reactions and molecular biology techniques. This method may also be applied to a variety of molecular biology reagents which may be contaminated with ribonuclease to protect an RNA from being degraded when incubated with the reagent.

Abstract: The invention features methods of diagnosing and treating Meniere disease. The invention also features kits and probes for diagnosing Meniere disease.

Abstract: A DNA sequence including a gene coding polypeptide having polyphenol oxidase (PPO) activity, or a fragment thereof.

Abstract: Novel nucleotide triphosphates, methods of synthesis and process of incorporating these nucleotide triphosphates into oligonucleotides, and isolation of novel nucleic acid catalysts (e.g., ribozymes) are disclosed. Also, described are the use of novel enzymatic nucleic acid molecules to inhibit HER2/neu/ErbB2 gene expression and their applications in human therapy.

Abstract: A polynucleotide molecule encoding human minor vault protein p193, or its complementary strands. A purified and isolated polynucleotide molecule consisting essentially of a nucleotide sequence encoding human minor vault protein p193, or its complementary strands, or a combination of a nucleotide sequence encoding human minor vault protein p193 and its complementary strands.

Abstract: A system for producing a library of oligomer comprising at least two monomers in a positionally determined array comprise a plurality of synthesis supports, a first plurality of support carriers wherein each carrier has a uniform array of distinct support holding positions for the synthesis supports; means for contacting each array of synthesis supports with a different monomer to provide a first chemical transformation of the synthesis supports; a second plurality of support carriers wherein each carrier has a uniform array of distinct support holding positions for receiving the chemically transformed synthesis supports contained in the first plurality of support carriers; transfer apparatus for transferring a selected row or column of synthesis supports from each of the first plurality of carriers to each of the second plurality of carriers to enable the supports in the second to undergo at least a second chemical transformation; and whereby each support position in each carrier identifies the chemical comp

Abstract: Novel nucleotide triphosphates, methods of synthesis and process of incorporating these nucleotide triphosphates into oligonucleotides, and isolation of novel nucleic acid catalysts (e.g., ribozymes) are disclosed. Also, described are the use of novel enzymatic nucleic acid molecules to inhibit HER2/neu/ErbB2 gene expression and their applications in human therapy.

Abstract: Novel nucleotide triphosphates, methods of synthesis and process of incorporating these nucleotide triphosphates into oligonucleotides, and isolation of novel nucleic acid catalysts (e.g., ribozymes) are disclosed.

Abstract: A labeled substance comprising a biological substance linked to a luminescent rhenium-containing label. Qualitative and quantitative electrochemiluminescent assays using the same. These methods comprise contacting a sample with a reagent labeled with an electrochemiluminescent chemical moiety containing rhenium and capable of combining with the analyte of interest, exposing the resulting sample to chemical, electrochemical, or electromagnetic energy and detecting electromagnetic radiation emitted by the electrochemiluminescent chemical moiety.

Abstract: The invention relates to oligoribonucleotide analogs with terminal 3′—3′ and/or 5′—5′ internucleotide linkages. This modification stabilizes the molecules altered in this way, including ribozymes, without adversely altering their properties, including, where appropriate, catalytic activities.

Abstract: The invention relates to Tango-71, Tango-73, Tango-74, Tango-76, and Tango-83 polypeptides, nucleic acid molecules encoding Tango-71, Tango-73, Tango-74, Tango-76, and Tango-83, and uses thereof.

Abstract: A nucleic acid molecule is provided which is initially catalytically inactive but which can complex with a specific co-factor, e.g., a nucleic acid molecule or a non-nucleic acid molecule, to form a catalytically active nucleic acid molecule. The catalytically active nucleic acid molecule can be used to detect the presence of a non-nucleic acid co-factor or of a nucleic acid co-factor using the nucleic acid sequence of the present invention.

Abstract: Methods are provided for the production of nucleic acid ligands against target molecules using a procedure known as Transcription-free Systematic Evolution of Ligands by EXponential enrichment (Transcription-free SELEX). The Transcription-free SELEX method assembles nucleic acid ligands from fragments of synthetic nucleic acids by annealing those fragments to a complementary template, and then ligating the fragments together.

Abstract: A compound having the formula: wherein, R1 represents 2′-O-R3-thio-R3 and/or 2′-C-R3-thio-R3, wherein R3 is a compound independently selected from a group consisting of alkyl, alkenyl, alkynyl, aryl, alkylaryl, carbocyclic aryl, heterocyclic aryl, amide and ester, X represents a base or H; Y represents a phosphorus-containing group; and R2 represents H, DMT or a phosphorus-containing group.

Abstract: The invention provides novel developmentally-regulated hippocampal genes and polypeptides encoded by those genes. The invention also provides expression vectors, host cells, and antibodies. The invention also provides methods for diagnosing, treating or preventing diseases associated with hippocampus.

Abstract: The present invention provides a method of treating bacterial respiratory infections by pulmonary administration of protonated/acidified nucleic acids. These modified nucleic acids are effective as bactericidal and/or bacteriostatic agents without regard to the class of bacteria, so are especially useful when diagnosis is difficult or when multiple infectious organisms are present. The antibiotic activity of nucleic acids of the invention is not dependent on either the specific sequence of the nucleic acid or the length of the nucleic acid molecule.