Abstract: Methods are provided for accurately predicting efficacy of chemotherapeutic agents. Methods of the invention increase the positive predictive value of chemosensitivity assays by assessing both the ability of a chemotherapeutic to destroy cells and the genetic propensity of those cells for resistance. Results obtained using methods of the invention provide insight into the in vivo effectiveness of a therapeutic, and lead to more effective chemotherapeutic treatment.
Abstract: Targeted sequencing of genetic regions that differ between two DNA preparations uses genomic fragment enrichment. This method can be used to study genetic variation among closely related species and microbial communities.
Type:
Grant
Filed:
December 27, 2005
Date of Patent:
August 11, 2009
Assignee:
The United States of America as represented by the U.S. Environmental Protection Agency
Inventors:
Orin C. Shanks, Jorge Santo Domingo, James E. Graham, Jingrang Lu
Abstract: Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI3), and an oligonucleotide form unusually stable hybrids with complementary target sequences, in which the tethered CDPI3 group resides in the minor groove of the duplex. These conjugates can be used as probes and primers. Due to their unusually high binding affinity, conjugates as short as 8-mers can be used as amplification primers with high specificity and efficiency. MGB conjugation also increases the discriminatory power of short oligonucleotides, providing enhanced detection of nucleotide sequence mismatches by short oligonucleotides.
Type:
Grant
Filed:
April 6, 2007
Date of Patent:
July 7, 2009
Assignee:
Epoch Biosciences, Inc.
Inventors:
Joel Hedgpeth, Irina A. Afonina, Igor V. Kutyavin, Eugeny A. Lukhtanov, Evgeniy S. Belousov, Rich B. Meyer, Jr.
Abstract: The invention relates to a method for artificial in vivo evolution of proteins, said method making it possible to bring about the evolution of a protein X by complementation of a relative protein Y, X and Y both belonging to the same class of enzyme commission (EC) nomenclature or belonging to related classes. The mutants D133E and R104Q of desoxycytidine kinase (DCK) were obtained; both of said mutations result in acquisition of thymidine kinase activity by DCK.
Type:
Grant
Filed:
May 19, 2005
Date of Patent:
June 16, 2009
Assignees:
Institut Pasteur, Centre National de la Recherche Scientifique (CNRS)
Inventors:
Philippe Marliere, Sylvie Pochet, Madeleine Bouzon
Abstract: The present invention provides methods and compositions for tagging nucleic acid sequence fragments, e.g., a set of nucleic acid sequence fragments from a single genome, with one or more unique members of a collection of oligonucleotide tags, or sequence tokens, which, in turn, can be identified using a variety of readout platforms. As a general rule, a given sequence token is used once and only once in any tag sequence. In addition, the present invention also provides methods for using the sequence tokens to efficiently determine variations in nucleotide sequences in the associated nucleic acid sequence fragments.
Abstract: The present invention relates to methods for precisely and effectively detecting mutations of organism.
Type:
Grant
Filed:
March 21, 2007
Date of Patent:
June 2, 2009
Assignee:
Genematrix, Inc.
Inventors:
Nam-Keun Kim, Suk-Joon Kim, Soo-Ok Kim, Eun-Ok Kim, Myung-Soon Moon, Wang-Don Yoo, Chang-Hong Lee, Hyun-Jae Chung, Mi-Sun Jee, Seong-Gyu Hwang, Sun-Pyo Hong
Abstract: The invention relates to methods for isolating and/or identifying nucleic acids. The invention also provides kits for isolating and/or identifying nucleic acids.
Abstract: The invention relates to compositions and methods for generating a signal indicative of the presence of a target nucleic acid in a sample utilizing a cleavage resistant probe.
Abstract: Methods of identifying the type of a cell are provided, the methods comprising determining the Tm profile of a sample rRNA or fragment thereof from the cell using a double stranded nucleic acid-specific dye, wherein a match between the determined Tm profile and the Tm profile of a corresponding rRNA or fragment thereof of a cell from a known cell type indicates that the sample rRNA is from the known cell type.
Type:
Grant
Filed:
June 4, 2007
Date of Patent:
April 28, 2009
Assignee:
University of Utah Research Foundation
Inventors:
Carl T. Wittwer, C. Wade Dummer, Virginie E. Dujols
Abstract: The present invention concerns processes for the detection and quantitation of nucleic acid molecules, polynucleotides, and/or oligonucleotides in a sample using hybridizationdetection assays, antibody-mediated recognition assays, nucleic acid sensor molecules, chromatographic assays, and/or electrophoresis assays. The present invention specifically concerns processes for the detection and quantitation of double stranded nucleic acid molecules, polynucleotides, and/or oligonucleotides in a sample using hybridization-detection assays. The nucleic acid molecules, polynucleotides, and/or oligonucleotides can include molecules that mediate RNA interference, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules.
Type:
Grant
Filed:
August 17, 2004
Date of Patent:
April 21, 2009
Assignee:
Sirna Therapeutics, Inc.
Inventors:
Susan Radka, Zinnen Shawn, Vasant Jadhav, James McSwiggen, Narendra Vaish
Abstract: Provided are methods of determining differences between nucleic acids in a test sample and a reference sample. In certain embodiments the methods are used for detecting and mapping chromosomal or genetic abnormalities associated with various diseases or with predisposition to various diseases, or to detecting the phenomena of large scale copy number variants. In particular, provided are advanced methods of performing array-based comparative hybridization that allow reproducibility between samples and enhanced sensitivity by using the same detectable label for both test sample and reference sample nucleic acids. Invention methods are useful for the detection or diagnosis of particular disease conditions such as cancer, and detecting predisposition to cancer based on detection of chromosomal or genetic abnormalities and gene expression level. Invention methods are also useful for the detection or diagnosis of hereditary genetic disorders or predisposition thereto, especially in prenatal samples.
Abstract: The present invention relates to methods for integrated ribonucleic acid integrity assessment and analysis comprising the steps of: (a) providing a support having immobilized thereon a set of detector probes and a set of at least two control probes, wherein (i) a first of said at least two control probes is complementary to 23S or 28S rRNA or a functionally equivalent RNA, and (ii) a second of said at least two control probes is complementary to 16S or 18S10 rRNA or a functionally equivalent RNA; (b) contacting said support with analyte ribonucleic acids derived from a sample, under conditions allowing hybridisation of complementary analyte ribonucleic acids and immobilized probes to form analyte ribonucleic acid/probe complexes; wherein said hybridisation generates a detectable signal; 15 (c) detecting signals generated by said complexes; (d) determining the ratio of signals generated by the 28S/control probe and 18S rRNA/control probe or 23S rRNA/control probe and 16S rRNA/control probe or functionally equi
Type:
Grant
Filed:
March 1, 2004
Date of Patent:
March 17, 2009
Assignee:
PamGene B.V.
Inventors:
Colin John Ingham, Richard Michael Anthony
Abstract: The invention relates to compositions and methods for detection of nucleic acid sequences. The invention further relates to kit format of said compositions for detection of nucleic acid sequences. Oligonucleotide probes of the invention comprise a target binding sequence and a sequence at least partially complementary thereto, joined by an optional linker to form a hairpin structure in the absence of the target nucleic acid sequence. The probes of the invention comprise a pair of moieties that produce a detectable signal when the probe hybridizes to the target sequence.
Type:
Grant
Filed:
February 9, 2006
Date of Patent:
March 17, 2009
Assignee:
Stratagene California
Inventors:
Scott B Happe, Joseph A Sorge, Andrew Firmin
Abstract: A method of determining the length of a polynucleotide target is provided. With this method, a target is first hybridized to an array of first probes having different, determined lengths, resulting in the formation of duplexes between the polynucleotide target and the first probes. These duplexes have a single stranded section of target if the target is longer than the first probe it is in a duplex with, and a single stranded section of probe if the target is shorter than the first probe it is in a duplex with. Next, a series of probes is hybridized to the duplexes, breaking apart duplexes in which the target and probe have unequal lengths through the process of branch migration. Thus, the target only remains bound in the duplex if the target and probe are of equal lengths. The length of the polynucleotide target can thereby be determined.
Type:
Grant
Filed:
April 24, 2007
Date of Patent:
March 10, 2009
Assignee:
The Board of Trustees of the Leland Stanford Junior University
Inventors:
Nader Pourmand, Ronald W. Davis, Shan X. Wang
Abstract: The present invention relates to a blotting method for rapidly analyzing nucleic acid comprising the steps of transferring a nucleic acid to be analyzed to the substrate and fixing the nucleic acid to be analyzed absorbed on the substrate; directing adding a nucleic acid probe to hybridize in a short time, without blocking the areas where the nucleic acid to be analyzed has not been fixed; removing the nucleic acid probe which has not been annealed to the nucleic acid to be analyzed by washing; and finally detecting the hybridization signal. According to the present invention, since the prehybridization is not needed and the hybridization and washing time is shortened, the time for the nucleic acid hybridization is dramatically shortened. Therefore, the whole blotting procedures for rapidly analyzing nucleic acid may be finished quickly.
Abstract: The present invention is directed to a method for adsorbing, i.e. non-covalently binding, nucleic acids to a solid phase using a two-step procedure. Furthermore, the present invention pertains to a method for isolating nucleic acids from a biological sample. In the first step of the procedure, lysis is effected by mixing the biological sample with an aqueous lysis buffer containing a chaotropic agent and incubating the mixture; in the second step, the concentration of the chaotropic agent in the mixture is increased and the mixture is contacted with the solid phase, whereby the nucleic acids in the liquid phase is adsorbed to the solid phase.
Type:
Grant
Filed:
February 18, 2005
Date of Patent:
February 17, 2009
Assignee:
Roche Diagnostics Operations, Inc.
Inventors:
Ralf Zielenski, Klaus Geissler, Thomas Walter
Abstract: The invention provides methods for sequencing a polynucleotide comprising stopping an extension cycle in a sequence by synthesis reaction before the reaction has run to near or full completion.
Type:
Grant
Filed:
October 26, 2006
Date of Patent:
February 17, 2009
Assignee:
Helicos BioSciences Corporation
Inventors:
Stanley Lapidus, Phillip Richard Buzby, Timothy Harris
Abstract: A method of detecting a target nucleic acid sequence comprising providing a stem-and-loop structured nucleic acid for measurement wherein the nucleic acid comprises complementary sequence portions located at both terminals and a target sequence portion therebetween as well as a double-stranded portion formed by hybridization of the complementary sequence portions located at both terminals and a remaining looped single-stranded portion, providing a probe nucleic acid having a sequence complementary to the target sequence portion wherein one end of the probe nucleic acid being immobilized to a solid substrate surface, reacting the nucleic acid for measurement with the probe nucleic acid to specifically hybridize the target sequence portion of the nucleic acid for measurement to the probe nucleic acid, and detecting presence or absence of the nucleic acid for measurement hybridized to the probe nucleic acid.
Abstract: The single nucleotide polymorphism analysis involves the utilization of a DNA hybridization process as well as the use of a DNA chip. A liquid DNA sample to be analyzed is guided over a DNA chip in a defined time course. After successful hybridization, the temperature is modified in a defined manner under low stringency conditions such that scavenger/target DNA hybrids are melted, whereby the melting of the scavenger/target DNA hybrids is detected and evaluated according to the temperature. In addition to the DNA chip, at least one device is provided that controls and regulates the temperature, and another device is provided that controls a lateral flow of liquid against the surface of the DNA chip. Factors for matching hybrids and mismatching/single point mismatching hybrids can be detected and evaluated using appropriate measuring device(s).
Type:
Grant
Filed:
May 28, 2004
Date of Patent:
February 10, 2009
Assignee:
Siemens Aktiengesellschaft
Inventors:
Walter Gumbrecht, Peter Paulicka, Manfred Stanzel
Abstract: The invention relates to a method of generating a signal indicative of the presence of a target nucleic acid in a sample, where the method includes forming a cleavage structure by incubating a sample comprising a target nucleic acid with a probe having a secondary structure that changes upon binding of the probe to the target nucleic acid and further comprising a binding moiety. The invention also includes the steps of cleaving the cleavage structure with a nuclease to release a nucleic acid fragment to generate a signal, wherein generation of the signal is indicative of the presence of a target nucleic acid in a sample, and detecting and/or measuring the amount of the fragment captured by binding of a binding moiety to a capture element on a solid support.