Abstract: The present invention relates to improved methods for the preparation of nucleic acids. More particularly, conventional solid supports used for nucleic acid synthesis are derivatized with activators having pKas within the 4 to 7 range. Preferentially, CPG-based solid supports are reacted with trialkoxysilanes containing an activator moiety such as pyridine. During each deblocking step of the nucleic acid synthesis cycle, bound pyridiniums are generated, yielding a weak acidic medium spreads throughout the solid support. The bound activators efficiently activate the phosphoramidite reagents towards coupling with 5?-hydroxynucleosides bound to the solid supports, thus eliminating or supplementing external deliveries of activator during the coupling steps.

Abstract: The present invention relates to a method for detecting and/or identifying Gram-positive bacteria with high GC content, in particular mycobacteria. The method comprises a nucleic acid amplification reaction and a subsequent hybridization reaction with suitable primers and probes. The invention furthermore relates to oligonucleotides, compositions, solid phases and kits which may be used for carrying out the method of the invention.

Abstract: A method of controlling the activity of a biologically active compound. The method concerns an oligonucleotide-based compound, comprising a hairpin-forming oligonucleotide, an effector moiety physically associated with the oligonucleotide, where the effector moiety possesses a biological activity, and a regulating moiety physically associated with the oligonucleotide, where the regulating moiety controls the biological activity of the effector moiety by interacting with the effector moiety. The oligonucleotide can assume a hairpin configuration, where the effector and regulating moieties interact, or an open configuration, where the effector and regulating moieties fail to interact. Depending on the nature of the effector and regulating moieties, either configuration can result in the expression of the biological activity of the effector moiety.

Abstract: Provided is a substrate for an oligomer probe array to which a photolabile material having an acetylene derivative is directly attached or attached via a linker.

Abstract: A method of easily releasing a useful substance bonded to oligonucleotide without impairing a target nucleic acid; and a novel base therefore. A nucleoside of nucleotide (oligonucleotide containing thereof) represented by the formula (I) (wherein each of X and Y independently represents —O—, —NH—, —N(alkyl)- or —S—; R represents a functional unit, a reporter unit or a biofunctional molecule; each of R1 and R2 independently represents a hydrogen atom, a phosphate bond group, a phosphoramidite group or a nucleotide; and n is a numeral of 1 to 10). There is further provided a method of releasing the R group moiety at base portion by the use of the oligonucleotide comprising the nucleotide.

Abstract: The present invention concerns oligonucleotides containing one or more modified nucleotides which increase the binding affinity of the oligonucleotides to target nucleic acids having a complementary nucleotide base sequence. These modified oligonucleotides hybridize to the target sequence at a faster rate than unmodified oligonucleotides having an identical nucleotide base sequence. Such modified oligonucleotides include oligonucleotides containing at least one 2?-O-methylribofuranosyl moiety joined to a nitrogenous base. Oligonucleotides can be modified in accordance with the present invention to preferentially bind RNA targets. The present invention also concerns methods of using these modified oligonucleotides and kits containing the same.

Abstract: Oligonucleotide conjugates, where an oligonucleotide is covalently attached to an aromatic system, are provided. In particular embodiments the oligonucleotide is complementary to the RNA component of human telomerase and is covalently attached to a nucleobase via an optional linker. The conjugates inhibit telomerase enzyme activity.

Abstract: An automated process for detecting the presence of a target nucleic acid in a sample. The process includes separating the target nucleic acid from other material present in the sample at a first station, transferring the separated target nucleic acid from the first station to a second station using a rotatable transport mechanism, combining the transferred target nucleic acid and reagents for performing an amplification reaction at the second station, and performing an amplification reaction. A product of the amplification reaction is detected as an indication of the presence of the target nucleic acid in the sample.

Abstract: An automated process for detecting the presence of a target nucleic acid in a sample. The process includes contacting a sample with a magnetically-responsive solid support and immobilizing a target nucleic acid present in the sample on the solid support. At a first station of an analyzer, the solid support is subjected to a magnetic field and the immobilized target nucleic acid is separated from a non-immobilized component of the sample. A solution comprising the separated target nucleic acid is moved to an incubator of a second station of the analyzer, where the separated target nucleic acid is subjected to an amplification procedure and an amplification product is formed. The amplification product is detected as an indication of the presence of the target nucleic acid in the sample.

Abstract: A method of characterizing a nucleic acid sample is provided that includes the steps of: (a) conducting a DNA polymerase reaction that includes the reaction of a template, an allele specific primer, at least one terminal phosphate-labeled nucleotide, DNA polymerase, and optionally an enzyme having 3??5? exonuclease activity when the primer is non-hydrolyzable, which reaction results in the production of labeled polyphosphate; (b) permitting the labeled polyphosphate to react with a phosphatase to produce a detectable species; (c) detecting the detectable species; and (d) characterizing the nucleic acid sample based on such detection.

Abstract: The present invention is related to compounds comprising mannitol or glucitol derivatives which may be used to build up oligomeric compounds. The invention is further related to uses of these oligomeric compounds for hybridization and as probes. In addition, methods for the detection of nucleic acids are disclosed wherein the oligomeric compounds are used.

Abstract: Diagnostic and therapeutic applications for certain types of cancer and precancerous conditions, including those deriving from hematologic cells, are described. Of particular interest are those cancers and precancerous conditions associated with increased signaling in the RAS-MAP kinase pathway. The diagnostic and therapeutic applications described herein are based on certain mutations in the protein tyrosine phosphatase gene PTPN11 and its expression product, PTPN11, promoting a gain-of-function in PTPN11 activity. Also described are nucleotide sequences, amino acid sequences, probes, and primers related to PTPN11 and PTPN11 variants, and cells expressing such variants.

Abstract: The present invention relates to a method of detecting or quantifying a target nucleic acid present in a specimen. The present invention provides a method of detecting or quantifying a target nucleic acid by using artificially-designed probes having a flag consisting of a plurality of units, thereby easily and accurately detecting the target nucleic acid.

Abstract: Compounds useful in the fluorescent labeling of biological materials are provided along with methods for their use and preparation.

Abstract: Compounds having structure (1) wherein R1 is —H a protecting group, a linker or a binding partner; and R2 and R34 are as defined in the specification. The invention also provides intermediates and methods make the structure (1) compounds, as well as methods to use the compounds as labels in diagnostic assays and to enhance binding to complementary bases.

Abstract: The present invention relates to a method of producing single-stranded nucleic acid molecules from oligo- or polynucleotides wherein each of said oligo- or polynucleotides has a predefined 5? or 3? terminus, comprising the steps of (a) annealing an adaptor oligonucleotide simultaneously or step by step to (aa) a first oligo- or polynucleotide; and (ab) a second oligo- or polynucleotide wherein the 5?-terminus of said adaptor oligonucleotide is complementary in sequence to the 5? terminus of said first oligo- or polynucleotide and the 3?terminus of said adaptor molecule is complementary in sequence to the 3? terminus of said second oligo- or polynucleotide; and optionally (a?) simultaneously with or subsequently to step (a) annealing at least one further adaptor oligonucleotide to free termini of said first or second oligonucleotides and to free termini of further oligo- or polynucleotides; (b) optionally filling in gaps between the neighbouring ends of said oligo- or polynucleotides; (c) ligating said oligo-

Abstract: An automated process for detecting the presence of a target nucleic acid in a sample. The process is performed in a stand-alone unit and includes separating the target nucleic acid from other material present in the sample, engaging a robotic pipettor to combine the separated target nucleic acid and reagents for performing an amplification reaction, and performing an amplification reaction. A product of the amplification reaction is detected as an indication of the presence of the target nucleic acid in the sample.

Abstract: The invention provides a novel method of labeling oligonucleotides, with reporter moieties, including but not limited to, quenchers, fluorophores, biotin, digoxigenin, peptides and proteins. In addition, this invention provides a method of detecting hybridization of oligonucleotides. This invention also provides novel azo quenchers having the general formula shown below. The invention further provides compositions comprising labeled oligonucleotides and solid supports. The invention also provides kits comprising at least one composition of the present invention.

Abstract: The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.

Abstract: Novel compounds are provided which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Ar—C(R1)(R2)—O—C(O)-wherein: Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous derivative thereof; R1 and R2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, optionally substituted aryl or optionally substituted heteroaromatic, or a vinylogous derivative of the foregoing; and X is a leaving group, a chemical fragment linked to Ar—C(R1)(R2)—O—C(O)— via a heteroatom, or a solid support; provided that when Ar is 1-pyrenyl and R1 and R2 are H, X is not linked to Ar—C(R1)(R2)—O—C(O)— via a nitrogen atom.

Abstract: This invention provides analyte sensitive oligonucleotide compositions for detecting and analyzing analytes in solution, including complex solutions using cross reactive arrays of analyte sensitive oligonucleotide compositions.

Abstract: A method to link a light emitting reporter to biomolecules with nucleotide oligomers is described. 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 particle generated by the methods 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: A method for detecting specific DNA sequences and discriminating single nucleotide polymorphisms (SNPs) using fluorescently labelled oligonucleotide probes is disclosed. Oligonucleotide probes are labelled with reporter molecules preferentially attached to an internal nucleotide residue. The fluorescence emission of oligonucleotide probes varies significantly when in single-stranded and double-stranded states despite the absence of quencher moieties, allowing reliable detection of complementary DNA targets. The melting temperature of probe/target duplexes permits discrimination of targets that differ by as little as a single nucleotide residue, such that polymorphic targets may be discriminated by fluorescence quantitation and Tm.

Abstract: The present invention discloses compounds and methods used to specifically target substrates of methylation by S-adenosyl-L-methionine (SAM)-dependent methyltransferases. The substrates can be peptides, single stranded nucleic acids or double stranded nucleic acids, including RNA, DNA and PNA or phospholipids. The compounds disclosed are SAM analogs that are ligated to a methylation site by the methyltransferase. Also disclosed, are reacting groups that are ligatable to the cofactor analogs and can also be used as detectable labels. The reacting group can be used to cleave the substrate providing a methylation footprint. The invention can be used clinically to determine methylation state of a gene or gene promoter such as those involved in imprinting and transcription. In some preferred embodiments, the invention includes a kit, which can include one or more suitable SAM analogs and may include one or more detectable labels. In other preferred embodiments, the invention includes a pharmaceutical composition.

Abstract: Methods, reagents and kits are provided for the production and use in detection assays of labeled nucleic acid molecules wherein a labeling molecule is attached directly to the 3? end of the nucleic acid molecules.

Abstract: The present invention provides compositions comprising oligonucleotides that have 3? end groups (e.g. lipophilic moieties) that are useful in invasive cleavage reactions such as the INVADER assay. Specifically, the present invention provides compositions containing oligonucleotides with 3? end groups configured for generating a detectable signal in invasive cleavages assays with a high signal-to-background ratio, as well as methods for generating such compositions.

Abstract: A method of identifying a base at a target position in a single-stranded sample DNA sequence, the method characterised by the steps of: (i) providing an oligonucleotide probe which is capable of hybridising to the sample DNA sequence such that the 3? nucleotide of the probe overlaps the target position, the probe being blocked at the 3? end to prevent extension by DNA polymerase but permitting 3?-5? exonuclease cleavage; (ii) incubating the sample DNA sequence with the probe in the presence of (a) a composition having 3?-5? exonuclease activity and (b) nucleotide triphosphates, under conditions that allow hybridisation of the probe to the sample DNA sequence; and (iii) detecting, directly or indirectly, cleavage of the 3? nucleotide of the probe.

Abstract: The invention provides molecules and methods for nucleic acid synthesis reactions useful in sequencing-by-synthesis processes.

Abstract: This disclosure provides novel reversibly terminated ribonucleotides which can be used as a reagent for DNA sequencing reactions. Methods of sequencing nucleic acids using the disclosed nucleotides are also provided.

Abstract: A hybridization method is provided in which an efficient hybridization reaction can be carried out. Further, there are provided, using this hybridization method, a method for detecting a target gene with high sensitivity and a signal amplifying method for markedly improving the detection sensitivity of the target gene. There is provided a hybridization method comprising the use of oligonucleotides in a reaction solution, the method comprising forming partially a reaction temperature region in the reaction solution and performing a hybridization reaction in the reaction temperature region.

Abstract: The present invention relates to novel nucleoside derivatives of general formula (I) wherein R1=H, halogen, NO2, CN, OCH3, an alkyl, alkoxy or alkoxyalkyl residue having 1 to 4 C atoms, preferably a methyl, ethyl, propyl or butyl residue or an optionally substituted aryl residue or aliphatic acyl residue having 2 to 5 atoms, R2 to R7=H, NO2, CN, OCH3, a branched or unbranched alkyl, alkoxy or alkoxyalkyl residue having 1 to 5 C atoms or an optionally substituted aryl residue or an aliphatic acyl residue having 2 to 5 atoms, X is the group C?O or C?S, Y?S, O, NR?, C(R?)2, wherein R? is H, or a branched or unbranched alkyl residue having 1 to 5 C atoms or an optionally substituted aryl residue, Z=SO2, OCO, OCS, SCS, and N is a nucleotide.

Abstract: The present invention relates to a process for labeling and purification of nucleic acids of interest present in a biological sample to be treated, comprising: taking a single reaction vessel, introducing into the reaction vessel: the biological sample, at least one labeling reagent for nucleic acids, at least one solid support enabling the adsorption of said nucleic acids, any ingredient necessary for the labeling of the nucleic acids and/or for the immobilization of said nucleic acids on the support, incubating the contents of the reaction vessel, and isolating the nucleic acids thus labeled. The invention finds a preferred application in the diagnostics field.

Abstract: A method for determining the sequence of at least a portion of a single-stranded nucleic acid molecule by base-specifically labeling the exposed bases of the nucleic acid molecule using heavy element-substituted nucleotide bases which form Watson-Crick type base-pairs with the exposed bases of the nucleic acid molecule and then imaging the labeled single-stranded nucleic acid molecule using electron microscopy, e.g., transmission electron microscopy (TEM), or some other method that permits discrimination of the heavy element substituted nucleotide bases is described. The image is analyzed to determine the base sequence of at least a portion of the nucleic acid molecule.

Abstract: Disclosed are methods for preparing particle-linked polynucleotides, and using the particle linked polynucleotides in genomic analysis. The particles as disclosed are characterized as having a size variance of less than 2%.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.

Abstract: To solve a problem occurring in the PALSAR method that a polymer would be formed in the state of unbound to a captured test gene and thus affect the quantitative characteristics as a nonspecific signal, it is intended to develop a technique whereby the polymer formation is controlled in the step of forming an assembly (polymer) of probes so that the polymer is formed exclusively on a test gene to thereby improve the sensitivity and quantitative characteristics. It is found that the polymer can be quantitatively formed and a nonspecific reaction can be inhibited by, in the step of forming a polymer by reacting plural kinds of probes having abilities to complementarily bind to each other, not adding or reacting these probes at once but starting with the reaction of a first probe in one group, and then reacting the second probe in the other group followed by the reactions of probes one by one (i.e., the first probe, the second probe, and so on).

Abstract: The present invention relates to compositions and methods for the preparation of modified nucleic acids. In particular, the present invention provides novel reagents and chemistries for the generation of linkers and modified phosphoramidates.

Abstract: Markers associated with Sclerotinia stem rot resistance are provided. Methods of identifying resistant, and susceptible plants, using the markers are provided. Methods for identifying and isolating QTL are a feature of the invention, as are QTL associated with Sclerotinia stem rot resistance.

Abstract: A method of making a set of labelled compounds by the use of a preferably particulate support, comprises dividing the support into lots, performing a different chemical reaction on each lot of the support, e.g. to couple a chemical moiety to that lot of the support, tagging a fraction of each lot of the support with a different label, and combining the said lots of the support. The steps are repeated several times, preferably to build up oligomer molecules carrying labels which identify the nature and position of a monomer unit of the oligomer, and which are releasable from the support. Preferred labels, which are releasable from the compounds by cleavage to provide charged groups for analysis by mass spectrometry, are groups of the trityl (trimethylphenyl) family. Also claimed are libraries of these labels and their use in assays and nucleic acid analysis methods.

Abstract: The invention relates to fluorescent N2,N3-etheno-purine (2?-deoxy) riboside derivatives and fluorescent oligonucleotide probes comprising one or more moieties thereof, their preparation and uses thereof for staining DNA/RNA and for detection and quantitation of genetic material.

Abstract: Embodiments of labeled nucleotide compositions are described. Methods are described in which a sample containing RNA is contacted with an enzyme having an RNA ligation activity in the presence of a labeled nucleotide composition to provide labeled RNA. Methods of performing an array analysis of a labeled RNA sample are also described.

Abstract: The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The structure-specific nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof. The present invention further relates to methods and devices for the separation of nucleic acid molecules based on charge. The present invention also provides methods for the detection of non-target cleavage products via the formation of a complete and activated protein binding region. The invention further provides sensitive and specific methods for the detection of human cytomegalovirus nucleic acid in a sample.

Abstract: The present invention relates to a kit and method for detecting M. tuberculosis of suspected patient. The present invention also relates to primers and probe used to detect M. tuberculosis by performing one tube nested PCR.

Abstract: The present invention relates to a temperature-stable labeling reagent of formula (0): in which: R1 represents H or an alkyl, aryl or substituted aryl group, R2 represents a detectable marker or at least two detectable markers interlinked by at least one multimeric structure, L is a linker arm comprising a linear chain of at least two covalent bonds and n is an integer equal to 0 or 1, R3 and R4 represent, independently of one another: H, NO2, Cl, Br, F, I, R2 —(L)n—Y—X—, OR, SR, NR2, R, NHCOR, CONHR, COOR, —CO—NH—(CH2)3—(O—CH2—CH2)3-CH2—NH—R2, —CO—NH—(CH2)3—(O—CH2—CH2)4—CH2—NH—R2 with R=alkyl or aryl, A is a linker arm comprising at least one covalent double bond enabling the conjugation of the diazo function with the aromatic ring and u is an integer between 0 and 2, preferably 0 or 1, —Y—X— represents —CONH—, —NHCO—, —CH2O—, —CH2S—, -Z-represents —NH—, —NHCO—, —CONH— or —O—, m is an integer between 1 and 10, preferably between 1 and 3, and p is an integer between 1 and 10, preferably between 1 and 3

Abstract: The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.

Abstract: The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.

Abstract: The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.

Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.

Abstract: The present invention relates to mutations in the gene coding for ferroportin 1 associated with hereditary haemochromatosis and methods for the diagnosis of hereditary haemochromatosis based on the identification of such mutations.

Abstract: The invention relates to the use of morpholino-nucleosides of formula: in which R1 represents a nucleic base and R2 represents a group corresponding to one of the following formulae: —(CH2)n—NH2 —(CH2)n—SH —(CH2)n—COOH —(CH2)n—OH —(CH2)n—NH—R3 —(CH2)n—SR3 —(CH2)n—CO—R3 —(CH2)n—OR3 in which n is an interger ranging from 1 to 12 and R3 is a group derived from a label, from a protein, from an enzyme, from a fatty acid or from a peptide, as chain terminators in a process of DNA or RNA sequencing by the Sanger method, or for the labelling of DNA or RNA fragments.