Abstract: The presently claimed invention provides for novel methods and kits for reducing the complexity of a nucleic acid sample by providing non-gel based methods for amplification of a subset of the sequences in a sample. In a preferred embodiment, amplification of a subset can be accomplished by digesting a sample with two or more restriction enzymes and ligating adaptors to the fragments so that only a subset of the fragments can be amplified. The invention further provides for analysis of the above amplified sample by hybridization to an array, which may be specifically designed to interrogate the desired fragments for particular characteristics, such as, for example, the presence or absence of a polymorphism.

Abstract: Releasable tag reagents for use in the detection and analysis of target molecules, particular in mass spectrometric analyzes are provided. Also provided are methods of detection that employ releasable tag reagents.

Abstract: The present invention relates to, for example, an ?-substituted ?-amino acid ester derivative asymmetric hydrolase including an enzyme of the following (a) or (b): (a) an enzyme comprising the amino acid sequence of SEQ ID NO:1 at least from position 1 to position 362, wherein the tyrosine at position 277 of SEQ ID NO:1 is substituted with alanine, tryptophan, isoleucine, or histidine, and having the ability to hydrolyze a substrate; or (b) an enzyme comprising the amino acid sequence of SEQ ID NO:1 at least from position 1 to position 362, wherein the tyrosine at position 277 of SEQ ID NO:1 is substituted with an amino acid other than tyrosine, and having the ability to hydrolyze a substrate.

Abstract: Aspects of the present invention include methods and compositions for determining the number of individual polynucleotide molecules originating from the same genomic region of the same original sample that have been sequenced in a particular sequence analysis configuration or process. In these aspects of the invention, a degenerate base region (DBR) is attached to the starting polynucleotide molecules that are subsequently sequenced (e.g., after certain process steps are performed, e.g., amplification and/or enrichment). The number of different DBR sequences present in a sequencing run can be used to determine/estimate the number of different starting polynucleotides that have been sequenced. DBRs can be used to enhance numerous different nucleic acid sequence analysis applications, including allowing higher confidence allele call determinations in genotyping applications.

Abstract: The invention relates to non-natural bases and base pairs that expand the normal DNA-based encoding system. Compositions herein may comprise at least one non-natural base that may interact with another base via a Watson Crick-type hydrogen bonding geometry and/or a Hoogsteen-type hydrogen bonding geometry. The bases may be used in a molecular entity, such as an oligomer or any other entity wherein the bases are attached to a backbone. For example, they may be comprised in DNA, RNA, or PNA, or a variety of other nucleic acid-type systems.

Abstract: Method for producing a modified oligonucleotide, wherein at least one polymer, preferably polyalkylene oxide, and/or a compound is covalently bound to the 5?-end or the 3?-end of the oligonucleotide via native ligation forming a native ligation site, with the proviso that the polymer and/or the compound is not a protein or peptide, if only the 5?-end of the oligonucleotide is modified by binding of the polymer or compound via native ligation. The invention is further directed to a modified oligonucleotide obtainable by the inventive method as well as the use of such modified oligonucleotide for the preparation of a medicament for preventing and/or treating a tumor, formation of metastasis, an immune disease or disorder, a cardiovascular disease or disorder, and/or a viral disease or disorder.

Abstract: A nucleic acid molecule can be annealed to an appropriate immobilized primer. The primer can then be extended and the molecule and the primer can be separated from one another. The extended primer can then be annealed to another immobilized primer and the other primer can be extended. Both extended primers can then be separated from one another and can be used to provided further extended primers. The process can be repeated to provide amplified, immobilized nucleic acid molecules. These can be used for many different purposes, including sequencing, screening, diagnosis, in situ nucleic acid synthesis, monitoring gene expression, nucleic acid fingerprinting, etc.

Abstract: This document provides methods and materials for assessing RNA expression. For example, methods and materials for detecting the presence, absence, or amount of target nucleic acid (e.g., target RNA or target cDNA produced from target RNA), kits for detecting the presence, absence, or amount of target nucleic acid (e.g., target RNA or target cDNA produced from target RNA), and methods for making such kits are provided.

Abstract: A protective group represented by the following general formula (I) (the oxygen atom attached with * represents oxygen atom of 2?-hydroxyl group of a ribonucleoside, a ribonucleotide or a derivative thereof; R1 and R2 both represent hydrogen atom, or represent a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group; R3 and R4 represent hydrogen atom, a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group; and R5 and R6 represent a halogen atom, a C1-6 halo-substituted alkyl group, cyano group, nitro group, or the like), which is stable under the reaction conditions of the nucleic acid synthetic cycles and has little steric hindrance, and can be removed under mild conditions using fluoride ions as a base.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Abstract: This invention relates to modified double-stranded oligoribonucleic acid (dsRNA) having improved stability in cells and biological fluids, and methods of making and identifying dsRNA having improved stability, and of using the dsRNA to inhibit the expression or function of a target gene.

Abstract: The profile of translation elongation rate along an mRNA is modulated in a directed manner by locally altering codon usage, in particular utilizing differences in ribosomal dwell times among pairs of synonymous codons translated by a single tRNA through wobble base pairing. Unlike codon optimization based on organism-specific codon frequencies or tRNA pools, the methods of the invention need not change the tRNA that translates the codon, rather modulating the interaction between a given tRNA and the mRNA coding sequence.

Abstract: A method of modulation of synthesis capacity on and cleavage properties of synthetic oligomers from solid support is described. The method utilizes linker molecules attached to a solid surface and co-coupling agents that have similar reactivities to the coupling compounds with the surface functional groups. The preferred linker molecules provide an increased density of polymers and more resistance to cleavage from the support surface. The method is particularly useful for synthesis of oligonucleotides, oligonucleotides microarrays, peptides, and peptide microarrays. The stable linkers are also coupled to anchor molecules for synthesis of DNA oligonucleotides using on support purification, eliminating time-consuming chromatography and metal cation presence. Oligonucleotides thus obtained can be directly used for mass analysis, DNA amplification and ligation, hybridization, and many other applications.

Abstract: Disclosed is a process for preparing a carbonucleoside of formula (1) and intermediates for use therein. The process involves the step of reacting a compound of formula (2) with a compound of formula (3) under Mitsunobu-type reaction conditions to obtain a compound of formula (4), wherein PG1, PG2, PG3 and PG4 are protecting groups. The compound of formula (4) is deprotected to form the compound of formula (1), as shown below.

Abstract: There is provided a high-sensitive Raman scattering sensing by regulating in metal nanoparticles for enhanced Raman scattering, particularly the strength of the enhanced electric field by controlling the distance between the particles to impart very strong Raman scattering properties. A metal nanoparticle material for molecular sensing, the metal nanoparticle material comprising: a metal nanoparticle aggregate including three to ten metal nanoparticles connected to each other through an organic molecule so that adjacent metal nanoparticles are bonded and spaced apart a predetermined distance, the aggregate containing a Raman active molecule within a field applied to the aggregate, wherein the metal nanoparticle material emits enhanced Raman scattering light from the Raman active molecule in an enhanced electric field; a method for producing the metal nanoparticle material for molecular sensing; and a molecular sensing by use of the metal nanoparticle material for molecular sensing.

Abstract: Compositions and methods for nucleic acid sequencing include template constructs that comprise double stranded portions in a partially or completely contiguous constructs, to provide for redundant sequence determination through one or both of sequencing sense and antisense strands, and iteratively sequencing the entire construct multiple times. Additional sequence components are also optionally included within such template constructs. Methods are also provided for the use and preparation of these constructs as well as sequencing compositions for their application.

Abstract: This invention relates to a peptide nucleic acid (PNA) oligomer which is conjugated with one or more linear-type amino acid containing a plurality of alkyleneglycols and to a synthesis method thereof. In addition, this invention related to a linear amino acid spacer in a device for detection for detecting a target gene using the PNA oligomers which is fixed on a surface of a functionalized solid support. The linear amino acid spacer contains a plurality of alkyleneglycols and maintains enough space between the solid support and PNA oligomer in the device in order to prevent the interference of the interaction between the PNA oligomer and a target gene. Furthermore, this invention relates to a PNA array, a PNA chip and a gene diagnosis kit whereof sensitivity and specificity are improved by being manufactured with the PNA conjugated with the amino acid spacer.

Abstract: The present disclosure relates to a set of at least 100 single-stranded oligonucleotide probes directed against (or complementary to) portions of a genomic target sequence of interest. The present disclosure also relates to a method of detecting a genomic target sequence of interest using the set of oligonucleotide probes and a method of generating the set of oligonucleotide probes. Further, the present disclosure relates to a kit comprising the set of oligonucleotide probes and at least one further component.

Abstract: The present invention provides methods of preparing an oligonucleotide, nucleoside or nucleoside analog for selective introduction into a subject's cells, the method comprising (1) selecting a targeted aptamer, internalizing nucleic acid or tumor-homing nucleic acid via iterative rounds of selection, and (i) hybridizing it to an oligonucleotide, (ii) replacing one or more nucleotide with a nucleoside or nucleoside analog, or (iii) synthesizing the it with one or more nucleoside or nucleoside analogs; or (2) preparing a naive combinatorial aptamer, internalizing nucleic acid or tumor-homing nucleic acid prodrug library, and running iterative rounds of selection for the cells. The present invention also provides the agent, the pharmaceutical composition, and methods of treating or preventing cancer and/or viral infection, the method comprising administration of the oligonucleotide, nucleoside or nucleoside analog for selective introduction into a subject's cells.

Abstract: Provided herein is method comprising: contacting an initial RNA sample containing a population of different RNA molecules with a divalent cation and a set of DNAzymes that are designed to cleave multiple target RNAs in the initial sample, thereby producing a product RNA sample that comprises: a) uncleaved RNA molecules and b) cleaved RNA fragments that contain a 2?,3?-cyclic-phosphate and a 5? hydroxyl as the result of DNAzyme cleavage.

Abstract: This invention relates to the use of tumor-derived or associated extracellular ribonucleic acid (RNA) found circulating in the plasma or serum fraction of blood for the detection, monitoring, or evaluation of cancer or premalignant conditions. Specifically, this invention enables the extraction of circulating RNA from plasma or serum and utilizes nucleic acid amplification assays for the identification, detection, inference, monitoring, or evaluation of any neoplasm, benign, premalignant, or malignant, in humans or other animals, which might be associated with that RNA. Further, this invention allows the qualitative or quantitative detection of tumor-derived or associated extracellular RNA circulating in the plasma or serum of humans or animals with or without any prior knowledge of the presence of cancer or premalignant tissue.

Abstract: An automated method for preparing and amplifying a sequence contained in a nucleic acid present in a sample, the nucleic acid being prepared in a receptacle that is part of a unit that includes a plurality of receptacles and holds a removable contact-limiting element for aspirating a fluid component of the sample from the receptacle.

Abstract: The present invention relates to unnatural base pairs of Ds (a 7-(2 thienyl)-3H-imidazo[4,5-b]pyridine-3-yl group) and a Pa derivative (a 2-nitro-1H-pyrrole-1-yl group bearing a substituent having a ?-electron system attached at position 4) that can be replicated with high selectivity/high efficiency, and methods for replicating nucleic acids containing the unnatural base pairs. The present invention also relates to methods for incorporating an unnatural base bearing a functional substituent attached thereto into DNA by a nucleic acid replication reaction. The present invention also relates to methods for replicating and selectively collecting a nucleic acid containing an unnatural base pair from a nucleic acid pool. The present invention also relates to methods for determining a sequence of natural bases in the proximity of an unnatural base in DNA for achieving highly efficient and highly selective replication of a nucleic acid containing the unnatural base.

Abstract: A method for synthesizing an oligonucleotide which comprises using a sulfurizing agent of general formula (I) for sulfurizing at least one phosphorus internucleotide linkage of a precursor of the oligonucleotide, wherein R is an aryl group or a heteroaryl group, which is bonded to the S-atom through an annular carbon atom; and R1 and R2 are independently organic residues, preferably a C1-C20 hydrocarbon residue. The method may further comprise purifying the oligonucleotide. Also included is a process for the synthesis of the sulfurizing agent.

Abstract: Provided is a crystallization process of cyclic adenosine 3?,5?-monophosphate, which comprises the following steps: 1) reacting an aqueous solution of cyclic adenosine 3?,5?-monophosphate with a base to obtain a salt of cyclic adenosine 3?,5?-monophosphate; 2) reacting the cyclic adenosine 3?,5?-monophosphate salt solution obtained in step 1) with an acid to obtain cyclic adenosine 3?,5?-monophosphate; 3) keeping cyclic adenosine 3?,5?-monophosphate obtained in step 2) at 0-15° C.

Abstract: Provided are improved processes and apparatuses for solid phase oligonucleotide synthesis, the improvements comprising carrying out detritylation of the nascent oligonucleotide using a composition of an organic solvent, a protic solvent and a selected concentration, or selected concentration range, of water. In some embodiments, an oligonucleotide synthesis apparatus includes means for adding water to a detritylation reagent. In some embodiments, an apparatus can include a water detector for analyzing the water concentration of a detritylation reagent to be reacted with a nascent oligonucleotide. An apparatus can comprise a feedback loop to control the concentration of water at the point of the detritylation reaction and/or to control the detritylation reaction time. The apparatuses and methods reduce batch-to-batch variations in the manufacture of oligonucleotides immobilized on the surface of various substrates.

Abstract: An apparatus and method for catalyzing a reaction on a substrate (24) comprising, a light source (12), a micromirror (16) positioned to redirect light (14) from the light source (12) toward a substrate (24) wherein the redirected light (14) catalyzes a chemical reaction proximate a substrate (24), is disclosed. A computer (18) is connected to, and controls, the positioning of mirrors within the micromirror (16) to specifically redirect light to specific portions of a substrate. The substrate (24) can be placed in a reaction chamber (50), wherein the light (14) that is redirected by the micromirror (16) catalyzes a chemical reaction proximate a substrate (24).

Abstract: The present invention concerns a method and a kit for the post-synthetic modification of nucleic acids via an inverse Diels-Alder reaction.

Abstract: The present invention relates to a method of forming a nanopore and a structure formed with the nanopore. The present invention relates to a method of forming a nanopore by preparing a first structure and a second structure having a surface on which nucleotides can be attached; attaching one ends of a plurality of oligonucleotides complementary to each other on the surface; binding the first structure and the second structure; and removing some of the bound oligonucleotides. The present invention is effective in that a pore of a desired size can be accurately formed by adjusting the length of the oligonucleotides.

Abstract: Polynucleotides and polypeptides which participate in influenza virus infection of cells and nucleic acid molecules, which include a polynucleotide sequence capable of specifically binding the polypeptides of the present invention. Also provided are methods of using such nucleic acid molecules, polynucleotides and antibodies directed thereagainst for diagnosing, treating and preventing influenza virus infection.

Abstract: The present application discloses an epigenetic marker for colon cancer.

Abstract: The present invention relates to certain novel shRNA molecules and methods of use thereof. According to certain embodiments of the present invention, methods for reducing the expression level of a target gene are provided. Such methods generally comprise providing a cell with one or more precursor nucleic acid sequences that encode two or more RNA molecules. A first RNA molecule comprises a double stranded sequence, which includes a guide strand sequence that is complementary to a portion of an mRNA transcript encoded by the target gene. In addition, a second RNA molecule comprises a second double stranded sequence, which includes a second guide strand sequence that is partially complementary to a portion of the mRNA transcript encoded by the target gene. Preferably, the second guide strand sequence comprises one or more bases that are mismatched with a nucleic acid sequence of the mRNA transcript encoded by the target gene.

Abstract: The present invention establishes a fast and simple [F-18] FLT synthesis process. Solid extraction units are used for purification to achieve an equally high and constant radiochemical yield and purity in a short period of time. By using a separation method, the impurities are reduced successfully while the total synthesis time is shortened. The radiochemical purity and the corrected radiochemical yield are both high.

Abstract: Libraries of nucleic acids encoding chimeric binding polypeptides based on plant scaffold polypeptide sequences. Also described are methods for generating the libraries.

Abstract: The present invention discloses preparation and application of double-stranded RNA molecules stable in mammalian body fluids. The mammalian-body-fluid-stable RNA molecules disclosed in the present invention are comprised of only unmodifide nucleotides. For the first time, the present invention discloses the applications of mammalian-body-fluid-stable RNA molecules for immunotherapy and siRNA drug development.

Abstract: Herein is reported a method for reducing the aggregation of an immunoglobulin in solution comprising the steps of i) comparing the amino acid sequence of the fourth framework region of the heavy chain of an antibody with a reference or germline sequence and determining whether one or more threonine residues and/or serine residues have been replaced by a different amino acid residue, and ii) modifying the amino acid sequence of the immunoglobulin by reverting the exchanged threonine residues and/or serine residues back to threonine or serine of the reference or germline sequence and thereby reducing the aggregation of an immunoglobulin in solution.

Abstract: The present invention provides multisignal labeling reagents and these are useful in a number of biochemical applications, including the manufacture of biomolecular probes and their use in detecting or amplifying analyte-specific moieties.

Abstract: The present invention provides multisignal labeling reagents and these are useful in a number of biochemical applications, including the manufacture of biomolecular probes and their use in detecting or amplifying analyte-specific moieties.

Abstract: The present invention is directed in part to a method for detecting a target nucleic acid using detector oligonucleotides detectable by mass spectrometry. This method takes advantage of the 5? to 3? nuclease activity of a nucleic acid polymerase to cleave annealed oligonucleotide probes from hybridized duplexes and releases labels for detection by mass spectrometry. This process is easily incorporated into a polymerase chain reaction (PCR) amplification assay. The method also includes embodiments directed to quantitative analysis of target nucleic acids.

Abstract: Oligonucleotide chemistry is central to the advancement of core technologies such as DNA sequencing, forensic and genetic analysis and has impacted greatly on the discipline of molecular biology. Oligonucleotides and their analogues are essential tools in these areas. They are often produced by automated solid-phase phosphoramidite synthesis but it is difficult to synthesize long DNA and RNA sequences by this method. Methods are proposed for ligating oligonucleotides together, in particular the use of an azide-alkyne coupling reaction to ligate the backbones of oligonucleotides together to form longer oligonucleotides than can be synthesized using current phosphoramidite synthesis methods.

Abstract: Inhibitors that can inhibit expression of FAM3B gene to reduce the levels of expression products, or can combine the expression products to reduce the activity of promoting lipid synthesis of FAM3B gene product are provided, wherein the inhibitors are one or more inhibitors selected from the group consisting of small interfering RNAs, antisense oligonucleotides, antibodies against FAM3B proteins and active organic compounds. Cells, vectors or inhibitor compositions, comprising such inhibitors, methods for inhibiting expression of FAM3B gene or inhibiting the activity of promoting lipid synthesis of FAM3B gene product using the inhibitors are provided. Methods for treating diseases mediated by expression of FAM3B gene using such inhibitors and uses of the inhibitors in preparing pharmaceuticals for preventing and/or treating the disease mediated by FAM3B gene expression are also provided.

Abstract: Oligonucleotide chemistry is central to the advancement of core technologies such as DNA sequencing, forensic and genetic analysis and has impacted greatly on the discipline of molecular biology. Oligonucleotides and their analogues are essential tools in these areas. They are often produced by automated solid-phase phosphoramidite synthesis but it is difficult to synthesize long DNA and RNA sequences by this method. Methods are proposed for ligating oligonucleotides together, in particular the use of an azide-alkyne coupling reaction to ligate the backbones of oligonucleotides together to form longer oligonucleotides that can be synthesized using current phosphoramidite synthesis methods.

Abstract: A conducting polymer including a conducting linker to connect a probe to the polymer, the linker including an unsaturated organic chain.

Abstract: Oligonucleotides with a novel sugar-phosphate backbone containing at least one 2?-arabino-fluoronucleoside and an internucleoside 3?-NH—P(?O)(OR)—O-5? linkage, where R is a positively charged counter ion or hydrogen, and methods of synthesizing and using the inventive oligonucleotides are provided. The inventive phosphoramidate 2?-aribino-fluorooligonucleotides have a high RNA binding affinity to complementary nucleic acids and are base and acid stable.

Abstract: The invention relates to [NiFe]-hydrogenases having an improved resistance to dioxygen, said [NiFe]-hydrogenases may be obtained by:—providing an initial polynucleotide comprising a sequence encoding a large subunit of a [NiFe]-hydrogenase, said large subunit comprising the following peptide motifs: •L1: RGXE, wherein X=L, I, F, V or M•L2: [R/K]X1C[G/R]X2C, wherein Xi is any amino acid residue, X2=L, V, I or M; L1 and L2 being separated by 16 any amino acid residues; •L3: X1X2X3X4X5X6X7X8X9X10X11X12[D/S/E], wherein X1=D, S, N or E, X2=H, D, S, N or L, X5=H, S, A, Q or W, X6=F, T, Y or G, X9=L, F, M or Y, the other Xn being any amino acid residue; •L4: D[P/I/S]CX1X2CX3X4[H/R], wherein X2=A, S, V, G or T, X1, X3 and X4 are any amino acid residue • and optionally comprising a motif LO: R[I/V/A]EG[H/D/A].—modifying said initial polynucleotide in order to substitute at least one of the residues X2 of motif L2 and Z or X4 of motif L3 and Z or X9 of motif L3 of said large subunit by a methionine.

Abstract: The invention features compositions and methods that are useful for reducing the expression or activity of a specified gene in eukaryotic cell.

Abstract: The present invention is directed to a method for producing a biomolecule conjugate where the method is integrated into a single unit operation.

Abstract: This invention provides compositions that have a light emitting reporter linked to biomolecules, preferably, nucleotide oligomers. The light reporter particles are silylated and functionalized to produce a coated light reporter particle, prior to covalently linking the biomolecules to the light reporter particle. The light reporter particles of the invention can be excited by a light excitation source such as UV or IR light, and when the biomolecule is DNA, the attached DNA molecule(s) are detectable by amplification techniques such as PCR.

Abstract: The invention is directed to a method of preparing a nucleic acid sequence with a modified splice site usage profile, which employs the use of a nucleic acid sequence comprising a cryptic splice donor site. The invention also provides a method of producing an alternate form of an RNA molecule encoded by a nucleic acid sequence, which nucleic acid sequence comprises a cryptic splice donor site, a heterologous nucleic acid sequence, and a splice acceptor site.

Abstract: The present invention provides labeled phospholink nucleotides that can be used in place of naturally occurring nucleotide triphosphates or other analogs in template directed nucleic acid synthesis reactions and other nucleic acid reactions and various analyzes based thereon, including DNA sequencing, single base identification, hybridization assays, and others.