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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 20344. Отображено 100.
12-01-2012 дата публикации

5'-modified bicyclic nucleic acid analogs

Номер: US20120010393A1
Принадлежит: ISIS PHARMACEUTICALS INC

The present invention provides 5′-modified bicyclic nucleoside analogs and oligomeric compounds comprising at least one of these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 5′-carbon. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including for example enhanced nuclease resistance.

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19-01-2012 дата публикации

Compositions and methods for detecting cryptococcus neoformans

Номер: US20120015362A1
Принадлежит: Medical Diagnostic Laboratories LLC

Disclosed are oligonucleotides useful in methods for determining whether a sample contains Cryptococcus neoformans , a causative agent for human cryptococcosis. These oligonucleotides, which have nucleotide sequences derived from a coding segment of the gene encoding the fungal specific transcription factor gene in Cryptococcus neoformans , are useful as forward and reverse primers for a polymerase chain reaction using nucleic acids from a biological sample as templates, and as probes for detecting any resultant amplicon. Detection of an amplicon indicates the sample contains Cryptococcus neoformans . Real-time PCR and detection using florescence resonance energy transfer is disclosed.

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19-01-2012 дата публикации

Method of immobilizing and stretching a nucleic acid on a substrate

Номер: US20120016110A1
Принадлежит: Individual

The present invention relates to a method of immobilizing and stretching a nucleic acid on a silicon substrate, to nucleic acids and substrates prepared according to this method, to uses of the method and to uses of the nucleic acid and the substrate.

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26-01-2012 дата публикации

Compositions and Methods for Induced Brown Fat Differentiation

Номер: US20120022500A1
Принадлежит: Dana Farber Cancer Institute Inc

The invention provides methods and compositions for inducing brown fat cell differentiation through modulation of both Prdm1β and C/EBPβ activity and/or expression. Also provided are methods for preventing or treating obesity or an obesity related disorder in a subject through stimulation of both Prdm1β and C/EBPβ expression and/or activity. Further provided are methods for identifying compounds that are capable of modulating both Prdm1β and C/EBPβ expression and/or activity.

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16-02-2012 дата публикации

Nucleotide analogs

Номер: US20120040340A1
Принадлежит: Helicos Biosciences Corp

The invention provides for nucleotide analogs and methods of using the same, e.g., for sequencing nucleic acids.

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01-03-2012 дата публикации

Methods of creating and screening dna-encoded libraries

Номер: US20120053091A1
Автор: Richard W. Wagner
Принадлежит: X Chem Inc

The present invention features a number of methods for identifying one or more compounds that bind to a biological target. The methods include synthesizing a library of compounds, wherein the compounds contain a functional moiety having one or more diversity positions. The functional moiety of the compounds is operatively linked to an initiator oligonucleotide that identifies the structure of the functional moiety.

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08-03-2012 дата публикации

Methods of using oligomeric compounds comprising 2'-substituted nucleosides

Номер: US20120059045A1
Принадлежит: ISIS PHARMACEUTICALS INC

The present disclosure provides oligomeric compounds comprising at least one 2′-fluoroethoxy modified nucleoside of formula I and methods of using these oligomeric compounds. The methods provided herein include contacting a cell or administering to an animal at least one of the oligomeric compounds. In certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

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15-03-2012 дата публикации

Il-17 homologous polypeptides and therapeutic uses thereof

Номер: US20120064073A1
Принадлежит: Individual

The present invention is directed to novel polypeptides having sequence identity with IL-17, IL-17 receptors and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided herein are methods for treating degenerative cartilaginous disorders and other inflammatory diseases.

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05-04-2012 дата публикации

Botulinum Neurotoxin B Receptors and Use Thereof

Номер: US20120082672A1
Принадлежит: Individual

It is disclosed here that synaptotagmin I (syt I) and synaptotagmin II (syt II) are the cellular receptors for botulinum neurotoxin B (BoNT/B) that mediate the cellular entry and toxicity of BoNT/B. The BoNT/B binding domains of syt I and II are also disclosed. While syt I needs gangliosides for BoNT/B binding, syt II can bind to BoNT/B in the absence of gangliosides. Various nucleic acids and polypeptides that relate to the BoNT/B binding domain of syt I or II are disclosed. Further disclosed are methods of reducing BoNT/B toxicity, methods of identifying agents that can block the binding between BoNT/B and syt I or II, methods of identifying agents that can bind to the BoNT/B binding domain of syt I or II, methods of detecting BoNT/B or Clostridium botulinum and kits for use thereof.

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19-04-2012 дата публикации

Derivatization of biomolecules by covalent coupling of non-cofactor compounds using methyltransferases

Номер: US20120094280A1
Принадлежит: BIOTECHNOLOGIJOS INSTITUTAS

The present invention relates to a use of non-cofactor compounds, represented by formulas (I) or (II) wherein R and Z are independently selected from H, D, C 1 -C 12 -alkyl, preferably C 1 -C 4 -alkyl, alkenyl, alkinyl, phenyl or -LX, wherein X represents a functional group or a reporter group attached via a linker group L, and QH is selected from —SH, —SeH, —NHNH 2 or —ONH 2 , for a targeted modification or derivatization of a biomolecule by covalent coupling to the biomolecule in the presence of a directing methyltransferase. Further development of the method of targeted modification and derivatization are the method for targeted labeling a biomolecule and method for detecting unmethylated target sites in a biomolecule comprising modification of the biomolecule according to the present invention.

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19-04-2012 дата публикации

Class ii human histone deacetylases, and uses related thereto

Номер: US20120094862A1
Принадлежит: Harvard College

The invention provides histone deacetylase class II nucleic acids and polypeptides, methods and reagents for their use, and related compounds including small molecule libraries containing class II histone deacetylase inhibitors.

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03-05-2012 дата публикации

Labelling Strategies for the Sensitive Detection of Analytes

Номер: US20120107943A1
Принадлежит: BASECLICK GMBH

The present invention relates to methods and reagents for detecting analytes, e.g. nucleic acids. The new methods and reagents allow a simple and sensitive detection even in complex biological samples.

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10-05-2012 дата публикации

Flow Chart Programming Platform for Testers and Simulators

Номер: US20120117537A1
Принадлежит: VELOCIO NETWORKS Inc

A system for the development, compilation, execution, monitoring and debug of automated test and simulation systems in a flow chart programming language. A development and debug system, implemented as software on a computer, which provides an application developer the capability to enter fully defined application programs through the use of graphical flow charts. An executions system, implemented as a program on a device incorporating a central processing unit, memory, communications and necessary interfaces, which executes graphical flow charts compiled by the development and debug system. The development and debug system communicates with the execution system to download programs, control operation, monitor operation and provide a debugging environment.

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17-05-2012 дата публикации

Method to enhance an immune response of nucleic acid vaccination

Номер: US20120121690A1
Принадлежит: Lipoxen Technologies Ltd

A composition comprising liposomes associated with a nucleic acid operatively encoding an antigenic protein and with an assistor protein, wherein the assistor protein shares at least one epitope with the antigenic protein, and wherein the nucleic acid and said assistor protein are associated with the same liposomes is described. The composition provides an improved immune response compared to mixtures of liposomes some of which are associated with the nucleic acid and some of which are associated with the assistor protein.

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17-05-2012 дата публикации

Rna sequence-specific mediators of rna interference

Номер: US20120122111A1
Принадлежит: Individual

The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.

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31-05-2012 дата публикации

Carbohydrate conjugates as delivery agents for oligonucleotides

Номер: US20120136042A1
Принадлежит: Alnylam Pharmaceuticals Inc

The present invention provides iRNA agents comprising at least one subunit of the formula (I): wherein: A and B are each independently for each occurrence O, N(R N ) or S; X and Y are each independently for each occurrence H, OH, a hydroxyl protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z′)(Z″)O-nucleoside, —P(Z′)(Z″)O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, —P(Z′)(Z″)O-Linker-OP(Z′″)(Z″″)O-oligonucleotide, a nucleotide, an oligonucleotide, —P(Z′)(Z″)-formula (I), —P(Z′)(Z″)— or -Linker-R; R is L G , -Linker-L G , or has the structure shown below: L G is independently for each occurrence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, polysaccharide; R N is independently for each occurrence H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl; and Z′, Z″, Z′″ and Z″″ are each independently for each occurrence O or S.

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14-06-2012 дата публикации

Methods and compositions for seamless cloning of nucleic acid molecules

Номер: US20120149069A1
Принадлежит: Life Technologies Corp

The present invention is in the fields of biotechnology and molecular biology. More particularly, the present invention relates to cloning or subcloning one or more nucleic acid molecules comprising one or more type IIs restriction enzyme recognition sites. The present invention also embodies cloning such nucleic acid molecules using recombinational cloning methods such as those employing recombination sites and recombination proteins. The present invention also relates to nucleic acid molecules (including RNA and iRNA), as well as proteins, expressed from host cells produced using the methods of the present invention.

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21-06-2012 дата публикации

Method for inducing extended self-renewal of functionally differentiated somatic cells

Номер: US20120156179A1
Автор: Michael Sieweke

The present invention relates to a method for inducing proliferation of functionally differentiated somatic cells comprising a step of activating expression of a Myc family gene and a KIf family gene in said cells or contacting said cells with a Myc family protein and a KIf family protein.

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21-06-2012 дата публикации

Preparation and isolation of 5' capped mrna

Номер: US20120156751A1
Принадлежит: APPLIED BIOSYSTEMS LLC

The synthesis of capped/tagged RNA, methods of use and kits providing same are contemplated. Tagged RNA permits isolation of RNA transcripts in vitro. The ability to isolate and purify capped RNA results in improved transcription and translation and provides a tool for identifying RNA-protein interactions. Such capped RNA finds use in therapeutic applications, diagnosis and prognosis and in the treatment of cancers and HIV.

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28-06-2012 дата публикации

Renewable chemicals and fuels from oleaginous yeast

Номер: US20120164701A1
Принадлежит: Solazyme Inc

The invention provides methods of cultivating oil-bearing microbes using xylose alone or in combination with other depolymerized cellulosic material. Also provided are microorganisms comprising an exogenous gene encoding a polysaccharide degrading enzyme, such as a cellulase, a hemicellulase, a pectinase, or a driselase. Some methods of microbial fermentation are provided that comprise the use of xylose and depolymerized cellulosic materials for the production of oil-bearing microorgansims.

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16-08-2012 дата публикации

Human platelet f11 receptor

Номер: US20120208990A1
Принадлежит: Individual

The present invention is directed to isolated nucleic acid molecules encoding human platelet F11 receptors. Expression vectors and host cells comprising the nucleic acid molecules are also provided, as well as methods for increasing or decreasing the expression of the human platelet F11 receptor in host cells. The invention further provides a method of screening a substance for the ability of the substance to modify human platelet F11 receptor function, and a method for isolating other human platelet F11 receptor molecules. DNA oligomers capable of hybridizing to the nucleic acid molecule encoding the human platelet F11 receptor are provided, which can be used to detect human platelet F11 receptor in a sample.

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16-08-2012 дата публикации

Bridged artificial nucleoside and nucleotide

Номер: US20120208991A1
Принадлежит: Osaka University NUC

It is an object of the present invention to provide a novel molecule for antisense therapies which is not susceptible to nuclease degradation in vivo and has a high binding affinity and specificity for the target mRNAs and which can efficiently regulate expression of specific genes. The novel artificial nucleoside of the present invention has an amide bond introduced into a bridge structure of 2′,4′-BNA/LNA. The oligonucleotide containing the 2′,4′-bridged artificial nucleotide has a binding affinity for a single-stranded RNA comparable to known 2′,4′-BNA/LNA and has an increased nuclease resistance over LNA. Particularly, it is expected to be applied to nucleic acid drugs because of its much stronger binding affinity for single-stranded RNAs than S-oligo's affinity

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23-08-2012 дата публикации

Modulation of factor 7 expression

Номер: US20120214862A1
Принадлежит: ISIS PHARMACEUTICALS INC

Disclosed herein are antisense compounds and methods for decreasing Factor 7 and treating or preventing thromboembolic complications in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 7 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Antisense compounds targeting Factor 7 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism.

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23-08-2012 дата публикации

Modified L-Nucleic Acid

Номер: US20120214868A1
Принадлежит: NOXXON PHARMA AG

A modified L-nucleic acid, containing an L-nucleic acid part conjugated to a non-L-nucleic acid part is described. The conjugate has extended retention time in and demonstrates a delayed elimination from an organism.

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30-08-2012 дата публикации

Process for triphosphate oligonucleotide synthesis

Номер: US20120220761A1
Принадлежит: Alnylam Pharmaceuticals Inc

The present invention describes simple, efficient, and enzyme-free method of making oligonucleotides with 5′-triphosphate. This invention presents novel process for synthesizing triphosphate oligonucleotides using a diaryl phosphonate as reagent. The process of the present invention is amenable to large-scale, economic 5′-triphosphate oligonucleotide synthesis.

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13-09-2012 дата публикации

Multi-targets interfering rna molecules and their applications

Номер: US20120232126A1
Принадлежит: Biomics Biotechnologies Co Ltd

This invention relates to interfering RNA (iRNA) molecules and their applications, especially multi-targets iRNA molecules and their applications. The said multi-targets iRNA molecules comprised of a sense strand annealed onto at least one antisense strand, each strand is at least 30 nucleotides in length, the sense or antisense strand has at least two segments, which can target at least two RNAs of different genes, or can target at least two portions of an RNA, and wherein the iRNA does not induce an interferon-response when transfected into a cell. The iRNA molecule can interfere with the translation procedure post-transcription, and the target gene is inhibited or blocked, the iRNA does not induce an interferon-response in vivo. The RNA molecules are the active ingredient in preparation of the drug which can regulate one or many genes function.

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04-10-2012 дата публикации

Compounds and pharmaceutical compositions for the treatment of viral infections

Номер: US20120251487A1
Автор: Dominique Surleraux
Принадлежит: IDENIX Pharmaceuticals LLC

Provided herein are compounds, compositions and methods for the treatment of liver disorders, including HCV infections. In one embodiment, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

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04-10-2012 дата публикации

Alpha-Amylase Variants

Номер: US20120252095A1
Принадлежит: Novozymes AS

The invention relates to a variant of a parent Termamyl-like alpha-amylase, comprising mutations in two, three, four, five or six regions/positions. The variants have increased stability at high temperatures (relative to the parent). The invention also relates to a DNA construct comprising a DNA sequence encoding an alpha-amylase variant of the invention, a recombinant expression vector which carries a DNA construct of the invention, a cell which is transformed with a DNA construct of the invention, the use of an alpha-amylase variant of the invention for washing and/or dishwashing, textile desizing, starch liquefaction, a detergent additive comprising an alpha-amylase variant of the invention, a manual or automatic dishwashing detergent composition comprising an alpha-amylase variant of the invention, a method for generating a variant of a parent Termamyl-like alpha-amylase, which variant exhibits increased.

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11-10-2012 дата публикации

Novel bacillus thuringiensis insecticidal proteins

Номер: US20120258910A1
Принадлежит: BAYER CROPSCIENCE NV

The invention pertains to novel insecticidal compounds derived from Bacillus thuringiensis strains. New proteins designated Cry2Ae, Cry2Af, and Cry2Ag, and variants thereof are provided, as well as DNA sequences encoding these proteins or their variants. Further provided are recombinant hosts expressing such proteins, particularly plant cells and plants.

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18-10-2012 дата публикации

Reversible platelet inhibition

Номер: US20120264815A1
Принадлежит: Duke University

The present invention relates, in general, to receptors and to platelet aggregation and, in particular, to a method of inhibiting platelet aggregation using an aptamer that binds to and inhibits the activity of a receptor, such as glycoprotein IIb/IIIa (gpIIb/IIIa), and to aptamers suitable for use in such a method. The invention also relates to antidotes to antiplatelet agents and to methods of using such antidotes to reverse aptamer-induced platelet inhibition. The invention further relates to von Willebrand Factor (VWF) inhibitors, and antidotes therefore, and to methods of using same.

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01-11-2012 дата публикации

Nucleic acid sequences encoding and compositions comprising ige signal peptide and/or il-15 and methods for using the same

Номер: US20120276142A1
Принадлежит: Individual

Fusion proteins and nucleic acid molecules encoding fusion proteins are disclosed. Fusion proteins comprising non-IL-15 signal peptide linked to IL-15 protein sequences and fusion proteins comprising an IgE signal peptide linked to non-IgE protein sequences are disclosed. Vectors comprising such nucleic acid molecules; and to host cells comprising such vectors are disclosed as well as recombinant vaccines and live attenuated pathogens encoding fusion proteins, and methods of using the same, are disclosed. The immunomodulatory effect following delivery of IL-15 and CD40L, with or without immunogens, is disclosed as are various nucleic acid molecules and compositions thereof used for delivering such proteins and methods of using such compositions.

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01-11-2012 дата публикации

Modulation of signal transducer and activator of transcription 3 (stat3)expression

Номер: US20120277284A1
Принадлежит: ISIS PHARMACEUTICALS INC

Disclosed herein are antisense compounds and methods for decreasing STAT3 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate hyperproliferative diseases.

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13-12-2012 дата публикации

Novel nucleic acid prodrugs and methods of use thereof

Номер: US20120316224A1
Принадлежит: Ontorii Inc

Described herein are nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties. Also described herein are methods of making and using nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties.

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20-12-2012 дата публикации

Synthesis of oligonucleotides

Номер: US20120322994A1
Принадлежит: Girindus AG

A method for preparing an oligonucleotide comprising the steps of a) providing a hydroxyl containing compound having the formula (A), b) reacting said compound with a phosphitylating agent in the presence of an activator (activator I) having the formula (I) to prepare a phosphitylated compound; and c) reacting said phosphitylated compound without isolation with a second compound having the formula (A) wherein R 5 , R 3 , R 2 , B are independently selected, but have the same definition as above in the presence of an activator II different from activator I.

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21-02-2013 дата публикации

Benzocyanine compounds

Номер: US20130045488A1
Принадлежит: Dyomics GmbH, Pierce Biotechnology Inc

Compounds useful as labels with properties comparable to known fluorescent compounds. The compounds are conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

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28-02-2013 дата публикации

Combinatorial library, a method for preparation of that combinatorial library, a method for sequence identification, a method for sequencing the elements of combinatorial libraries of oligonucleotides and/or oligonucleotide analogues, the use of a linker to generate combinatorial libraries and a sequence identification set

Номер: US20130053258A1
Принадлежит: INSTYTUT CHEMII BIOORGANICZNEJ PAN

The invention provides a combinatorial library, a method for preparation of that combinatorial library, a method for sequence identification, a method for sequencing the elements of combinatorial libraries of oligonucleotides and/or oligonucleotide analogues, the use of a linker to generate combinatorial libraries and a sequence identification set. More precisely, the objective of the invention is the ability to “read” sequences of selected elements of combinatorial libraries of freely modified synthetic oligonucleotides. The solution may be used both for researching for leading compounds in the pharmaceutical industry, and as a tool for studying the properties of oligonucleotides in the aspect of their potential use in experimental antisense or antigen therapy. The invention develops an appropriate strategy for determining the structure of isolated library elements, as usefulness of the combinatorial library depends on the ability to recognize the structure of its elements. Thanks to the developed and presented method for sequencing combinatorial oligonucleotide libraries it is possible to indisputably identify the sequences of biologically active elements selected by the combinatorial synthesis method.

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07-03-2013 дата публикации

In vivo gene regulation by the combination of knock-in-teto sequence into the genome and tetracycline-controlled trans-suppressor (tts) protein

Номер: US20130061343A1
Автор: Kenji Tanaka, Rene Hen
Принадлежит: Columbia University of New York

Disclosed is a FAST (Flexible Accelerated STOP TetO-knockin) system, an efficient method for manipulating gene expression in vivo to rapidly screen animal models of disease. This invention further discloses a single gene targeting event yielding 2 distinct knockin mice—STOP-tetO and tetO knockin—which permit generation of multiple strains with variable expression patterns: 1) knockout, 2) Cre-mediated rescue; 3) tTA-mediated misexpression; 4) tTA-mediated overexpression; and 5) tTS-mediated conditional knockout/knockdown. Using the FAST system, multiple gain- and loss-of-function strains can therefore be generated on a timescale not previously achievable. These strains can then be screened for clinically-relevant abnormalities. The flexibility and broad applicability of the FAST system is demonstrated by targeting several genes encoding proteins implicated in neuropsychiatric disorders: Mlc1, Neuroligin 3, the serotonin 1A receptor, and the serotonin 1B receptor.

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21-03-2013 дата публикации

RETINOID-LIPOSOMES FOR ENHANCING MODULATION OF HSP47 EXPRESSION

Номер: US20130071478A1
Принадлежит:

What is described are pharmaceutical compositions comprising a double-stranded nucleic acid molecule comprising a sense strand and an antisense strand wherein the sense and antisense strands are selected from the oligonucleotides described as SERPINH (SEQ ID NOS: 60 and 127), SERPINH(SEQ ID NOS: 98 and 165), and SERPINH (SEQ ID NOS: 101 and 168), and drug carrier comprising a mixture of a retinoid and a lipid vesicle, and methods of using these pharmaceutical compositions to treat a disease associated with hsp47 espresssion, including fibrosis. 1. A pharmaceutical composition comprising a drug carrier and a double-stranded nucleic acid molecule , wherein the drug carrier comprises a stellate cell-specific amount of a retinoid , and wherein the double-stranded nucleic acid molecule comprises the structure:{'br': None, 'sub': 'x', '5′(N)—Z 3′ (antisense strand)'}{'br': None, 'sub': 'y', '3′Z′—(N′)-z″ 5′ (sense strand)'}wherein each of N and N′ is a nucleotide which may be unmodified or modified, or an unconventional moiety;{'sub': x', 'y, 'wherein each of (N)and (N′)is an oligonucleotide in which each consecutive N or N′ is joined to the next N or N′ by a covalent bond;'}wherein each of Z and Z′ is independently present or absent, but if present independently includes 1-5 consecutive nucleotides or non-nucleotide moieties or a combination thereof covalently attached at the 3′-terminus of the strand in which it is present;{'sub': 'y', 'wherein z″ may be present or absent, but if present is a capping moiety covalently attached at the 5′-terminus of (N′);'}wherein each of x and y is independently an integer between 18 and 40;{'sub': y', 'x, 'wherein the sequence of (N′)has complementary to the sequence of (N); and'}{'sub': 'x', 'wherein (N)includes an antisense sequence to the mRNA coding sequence for human hsp47 exemplified by SEQ ID NO:1.'}212145151a. The pharmaceutical composition of claim 1 , wherein the siRNA comprises oligonucleotide sequences selected from the ...

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21-03-2013 дата публикации

NOVEL SHRNA MOLECULES AND METHODS OF USE THEREOF

Номер: US20130071928A1
Автор: Rao Donald
Принадлежит: GRADALIS, INC.

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. 1. A method for reducing the expression level of a target gene , which comprises providing a cell with one or more bifunctional RNA molecules , wherein:a first RNA molecule comprises a first double stranded sequence, which comprises a first guide strand sequence that is fully complementary to a passenger strand and an mRNA transcript encoded by the target gene; anda second RNA molecule comprises a second double stranded sequence, which comprises a second guide strand sequence that is complementary to the mRNA transcript encoded by the target gene, wherein the second guide strand sequence comprises one or more bases that are mismatched with a passenger strand and fully complementary to a nucleic acid sequence of the mRNA transcript encoded by the target gene; wherein the bifunctional RNA molecule activates cleavage-dependent and cleavage-independent RNA-induced silencing complex for reducing the expression level of the target gene.2. The method of claim 1 , wherein the first and second double stranded sequences reside within a stem portion of two ...

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21-03-2013 дата публикации

USE OF TOLL-LIKE RECEPTOR-9 AGONISTS, TOLL-LIKE RECEPTOR-4 ANTAGONISTS, AND/OR NUCLEAR OLIGOMERIZATION DOMAIN-2 AGONISTS FOR THE TREATMENT OF PREVENTION OF TOLL-LIKE RECEPTOR-4-ASSOCIATED DISORDERS

Номер: US20130072547A1

The present invention relates to the use of a TLR9 agonist and/or a TLR4 antagonist and/or a NOD2 agonist for treatment or prevention of disorders involving TLR4 activation, such as systemic sepsis and necrotizing enterocolitis. 1. A method of reducing the risk of an infant developing necrotizing enterocolitis comprising administering , to the infant , an effective amount of a TLR9 agonist.2. The method of claim 1 , wherein the TLR9 agonist is an oligonucleotide comprising an unmethylated CpG dinucleotide. This application is a continuation of U.S. patent application Ser. No. 12/104,816 filed Apr. 17, 2008, and claims priority to U.S. Provisional application Ser. No. 60/912,862 filed Apr. 19, 2007, and to U.S. Provisional application Ser.No. 61/027,728 filed Feb. 11, 2008, the contents of each of which are hereby incorporated by reference in their entireties herein, and to each of which priority is claimed.The TLR4 and TLR9 -related subject matter of this specification was developed, at least in part, under National Institutes of Health Grant No. R01-GM078238-01, so that the United States Government has certain rights herein. No federal funds were used in the development of subject matter related to NOD2.The present invention relates to the use of a Toll-like receptor-9 (TLR9) agonist and/or a Toll-like receptor-4 (TLR4) antagonist and/or a Nuclear Oligomerization Domain-2 (NOD2) agonist for treatment or prevention of disorders involving Toll-like receptor-4 (TLR4) activation, such as systemic sepsis and necrotizing enterocolitis. It is based, at least in part, on the discovery that a TLR9 agonist, a TLR4 antagonist, and a NOD2 agonist can suppress the consequences of TLR4 activation in such conditions.Necrotizing enterocolitis (“NEC”) is the most common—and most lethal—disease affecting the gastrointestinal tract of premature infants. It has become more common as the survival rate of premature infants has improved, and is diagnosed at an incidence of between 0.09 ...

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21-03-2013 дата публикации

RNA SYNTHESIS-PHOSPHORAMIDITES FOR SYNTHETIC RNA IN THE REVERSE DIRECTION, AND APPLICATION IN CONVENIENT INTRODUCTION OF LIGANDS, CHROMOPHORES AND MODIFICATIONS OF SYNTHETIC RNA AT THE 3'-END

Номер: US20130072670A1
Принадлежит: ChemGenes Corporation

The present invention relates to novel phosphoramidites, A-n-bz, C-n-bz, C-n-ac, G-n-ac and U are produced with an HPLC purity of greater than 98% and P NMR purity greater than 99%. A novel process of reverse 5′→3′ directed synthesis of RNA oligomers has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%. 2. The process according claim 1 , wherein L is cholesterol with the linker or the spacer claim 1 , and n=19.3. The process according to claim 1 , wherein L is polyethyleneglycol (PEG) claim 1 , and n=19.4. An RNA oligonucleotide claim 1 , wherein the RNA oligonucleotide is synthesized by the process according to . This application is a continuation application to U.S. application Ser. No. 12/584,625, filed Sep. 8, 2009, which in turn claims priority to U.S. Provisional Application Ser. No. 61/191,065, filed on Sep. 6, 2008. The entire teachings of the above applications are incorporated herein by reference.This invention relates to the synthesis of novel RNA monomer phosphoramidites, and corresponding solid supports that are suitable for a novel method of RNA oligonucleotide synthesis in reverse 5′→3′ direction. This approach leads to very clean oligonucleotide synthesis allowing for introduction of various modifications at the 3′-end cleanly and efficiently in order to produce high purity and therapeutic grade RNA oligonucleotides.Defined sequence RNA synthesis in the 3′→5′ direction is now well established and currently in use for synthesis and development of a vast variety of therapeutic grade RNA aptamers, tRNAs, siRNA and biologically active RNA molecules. This approach utilizes a ribonucleoside with suitable N-protecting group: generally 5′-Protecting group, the most popular being dimethoxytriphenyl, i.e. the DMT group; 2′-protecting group, out of which most popular is t-Butyldimethylsilyl ether; and, a 3′-phosphoramidite, the most popular of which is cyanoethyl diisopropyl ( ...

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21-03-2013 дата публикации

Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure

Номер: US20130072671A1
Принадлежит: Leids Universitair Medisch Centrum LUMC

The invention provides a method for generating an oligonucleotide with which an exon may be skipped in a pre-mRNA and thus excluded from a produced mRNA thereof. Further provided are methods for altering the secondary structure of an mRNA to interfere with splicing processes and uses of the oligonucleotides and methods in the treatment of disease. Further provided are pharmaceutical compositions and methods and means for inducing skipping of several exons in a pre-mRNA.

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21-03-2013 дата публикации

Nitrogen Responsive Early Nodulin Gene

Номер: US20130074214A1

Isolated nucleic acids and proteins and plants expressing the same for improved nitrogen utilization, increased yield, and increased stress tolerance.

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21-03-2013 дата публикации

Soybean Transgenic Event MON87705 and Methods for Detection Thereof

Номер: US20130074224A1
Принадлежит: MONSANTO TECHNOLOGY LLC

The present invention provides a transgenic soybean event MON87705, and cells, seeds, and plants comprising DNA diagnostic for the soybean event. The invention also provides compositions comprising nucleotide sequences that are diagnostic for said soybean event in a sample, methods for detecting the presence of said soybean event nucleotide sequences in a sample, probes and primers for use in detecting nucleotide sequences that are diagnostic for the presence of said soybean event in a sample, growing the seeds of such soybean event into soybean plants, and breeding to produce soybean plants comprising DNA diagnostic for the soybean event. 1. A soybean plant comprising a DNA molecule comprising a polynucleotide having a sequence that is or is complementary to two or more sequences selected from the group consisting of SEQ ID NOs: 1 , 2 and 18.2. A plant part of the soybean plant of claim 1 , wherein said plant part comprises a polynucleotide having a sequence that is or is complementary to two or more sequences selected from the group consisting of SEQ ID NOs: 1 claim 1 , 2 and 18.3. Progeny of the soybean plant of claim 1 , wherein said progeny comprises a polynucleotide having a sequence that is or is complementary to two or more sequences selected from the group consisting of SEQ ID NOs: 1 claim 1 , 2 and 18.48.-. (canceled)9. A DNA molecule comprising a polynucleotide having a sequence that is or is complementary to one selected from the group consisting of sequences listed under SEQ ID NOs: 2 and 18.10. An isolated DNA molecule comprising at least from about 11 to about 20 consecutive nucleotides selected from SEQ ID NO: 1 or SEQ ID NO: 2.11. A genome of a soybean cell comprising a polynucleotide having a sequence selected from the group consisting of two or more sequences listed under SEQ ID NOs: 1 claim 1 , 2 and 18.1221.-. (canceled)22. A composition having a DNA molecule consisting of two or more sequences selected from the group consisting of SEQ ID NOs: 1 ...

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28-03-2013 дата публикации

NOVEL SHRNA MOLECULES AND METHODS OF USE THEREOF

Номер: US20130078719A1
Автор: Rao Donald
Принадлежит: GRADALIS, INC.

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. 1. A bifunctional RNA molecule comprising:a first double stranded sequence comprising a guide strand sequence that is fully complementary to a passenger strand and an mRNA transcript encoded by the target gene; anda second double stranded sequence that is partially complementary to a mismatched passenger strand and complementary to the mRNA transcript encoded by the target gene, wherein the bifunctional RNA molecule activates cleavage-dependent and cleavage-independent RNA-induced silencing complex for reducing the expression level of the target gene.2. The bifunctional RNA molecule of claim 1 , wherein the first and second double stranded sequences reside within a stem portion of two or more stem loop structures.3. The bifunctional RNA molecule of claim 1 , wherein the first guide strand sequence is presented to a cleavage dependent RNA-induced silencing complex and binds to an mRNA transcript encoded by the target gene.4. The bifunctional RNA molecule of claim 3 , wherein the binding of the first guide strand sequence to the mRNA transcript ...

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28-03-2013 дата публикации

FORMULATIONS COMPRISING ANTISENSE NUCLEOTIDES TO CONNEXINS

Номер: US20130079388A1
Принадлежит: CoDa THERAPEUTICS, INC.

A therapeutic and/or cosmetic formulation comprising at least one anti-sense polynucleotide to a connexin protein together with a pharmaceutically acceptable carrier or vehicle is useful in site specific down regulation of connexin protein expression, particularly in reduction of neuronal cells death, wound healing, reduction of inflammation, decrease of scar formation and skin rejuvenation and thickening. 1. A pharmaceutical composition for use in therapeutic or cosmetic treatment , the formulation comprising an immunostimulatory anti-connexin 43 oligonucleotide.2. The pharmaceutical composition of claim 1 , wherein the immunostimulatory anti-connexin 43 oligonucleotide comprises a sequence having homology with SEQ ID NO: 1 and SEQ ID NO:2 and comprises at least 2 CpG sequence motifs.3. The pharmaceutical composition of wherein the immunostimulatory anti-connexin 43 oligonucleotide comprises SEQ ID NO: 13 or SEQ ID NO: 14 claim 2 , or an anti-connexin 43 oligonucleotide comprising at least 2 CpG motif sequences and having at least 70% homology to SEQ ID NO: 1 or SEQ ID NO:2.4. A method of treating a subject having a wound claim 2 , comprising administering to the wound an amount of a connexin 31.1 antisense polynucleotide effective to promote wound healing.5. A pharmaceutical composition comprising a connexin 43 antisense polynucleotide and a nonionic polyoxyethylene-polyoxypropylene copolymer claim 2 , wherein said connexin 43 antisense polynucleotide is an oligonucleotide provided in an amount effective to reduce connexin expression.6. A pharmaceutical composition according to which is formulated for topical administration.7. A pharmaceutical compound according to wherein which comprises said composition comprises an amount of antisense polynucleotide sufficient for treatment of a wound.8. A pharmaceutical composition according to formulated with a connexin antisense polynucleotide in an amount sufficient to downregulate the expression of a connexin protein in a ...

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28-03-2013 дата публикации

siRNA And Their Use In Methods And Compositions For The Treatment And/Or Prevention Of Eye Conditions

Номер: US20130079389A1
Принадлежит: SYLENTIS S.A.U.

The invention relates to methods and compositions for the treatment/and or prevention of eye conditions related to high levels of expression and/or activity of the vanilloid-1 receptor (TRPV). 1. A method of treating an eye condition characterized by increased expression and/or activity of IRPV1 , said method comprising topically administering to the corneal surface of the eye of a patient in need thereof a short interfering ribonucleic acid (siRNA) molecule wherein said molecule specifically targets SEQ. ID NO: 1.2. The method according to claim 1 , wherein said eye condition is ocular pain.3. The method according to claim 1 , wherein said eye condition is selected from the group consisting of altered sensitivity following refractive surgery claim 1 , use of contact lenses claim 1 , dry eye syndrome claim 1 , and Sjogren's syndrome.4. The method according to claim 1 , wherein said siRNA comprises a 19 nucleotide double-stranded structure.5. The method according to wherein said siRNA is blunt-ended.6. A method of treating an eye condition comprising topically administering to the corneal surface of the eye of a patient in need thereof an siRNA molecule wherein said molecule specifically targets SEQ ID NO: 1 and reduces expression of TRPV1 gene when introduced in a cell and wherein said siRNA comprises a 19 nucleotide blunt-ended double-stranded structure.7. The method according to claim 1 , wherein said siRNA comprises SEQ ID NO:2.8. The method according to claim 1 , wherein at least one nucleotide of said siRNA molecule comprises a chemical modification.9. The method according to claim 8 , wherein said chemical modification of said at least one nucleotide is selected from the group consisting of 2′-O-Methylation claim 8 , substitution of uracyl ribose nucleotides with deoxythymidine nucleotides claim 8 , and combinations thereof.10. The method according to claim 8 , wherein said chemical modification is on the sense strand claim 8 , the antisense strand or on both ...

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28-03-2013 дата публикации

NUCLEIC ACID MOLECULES, POLYPEPTIDES, ANTIBODIES AND COMPOSITIONS FOR TREATING AND DETECTING INFLUENZA VIRUS INFECTION

Номер: US20130079390A1
Принадлежит: Yeda Research and Development Co. Ltd.

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. 1. An isolated nucleic acid aptamer molecule comprising a polynucleotide sequence capable of specifically binding a polypeptide participating in influenza virus infection of cells , wherein said polynucleotide binds a region of hemagglutinin defined by amino acid coordinates 91-261 of SEQ ID NO: 1.2. The isolated nucleic acid aptamer molecule of claim 1 , wherein said polynucleotide sequence is selected from the group consisting of SEQ ID Nos. 11 and 12.3. The isolated nucleic acid aptamer molecule of claim 1 , wherein said polynucleotide sequence is single stranded.4. The isolated nucleic acid aptamer molecule of claim 1 , wherein said polynucleotide sequence is DNA or modifications thereof.5. The isolated nucleic acid aptamer molecule of claim 1 , wherein said polynucleotide sequence is RNA or modifications thereof.6. The isolated nucleic acid aptamer molecule of claim 1 , further comprising a detectable label.7. The nucleic acid aptamer molecule of claim 1 , wherein said polynucleotide sequence includes 2′-fluoro (2′-F) modified nucleotides.8. The nucleic acid aptamer molecule of claim 1 , wherein said polynucleotide sequence is selected having a length between 10 to 35 nucleotides.9. The nucleic acid aptamer molecule of claim 1 , wherein said polynucleotide is conjugated to a high molecular weight carrier.10. The nucleic acid aptamer molecule of claim 1 , wherein said high molecular weight carrier comprises PEG.11. A method of generating the aptamer molecule capable of claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) ...

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28-03-2013 дата публикации

METHOD FOR DESIGNING A DRUG REGIME FOR HIV-INFECTED PATIENTS

Номер: US20130079506A1
Принадлежит: Virco BVBA

The instant disclosure describes a novel genotype and phenotype assay to elucidate and/or evaluate new potential HIV integrase inhibitors, but also currently approved and experimental compounds that target protease, reverse transcriptase, and RNaseH. This assay allows studying linked mutations and mutational patterns that occur under HAART and experimental therapies. 1. (canceled)2. A primer having a nucleotide sequence consisting of any one of SEQ ID NOs: 1-10 , 53 , and 54.3. The primer of claim 2 , wherein said primer consists of the polynucleotide sequence of any one of SEQ ID NOs: 1-10 claim 2 , 53 claim 2 , and 54.4. A set of primers for producing a DNA copy of a segment of an HIV genome comprising the primers having the polynucleotide sequence of any one of SEQ ID NOs: 1-10 claim 2 , 53 claim 2 , and 545. The set of primers of comprising primers having the polynucleotide sequence of: SEQ ID NO: 1 claim 4 , SEQ ID NO: 2 claim 4 , SEQ ID NO: 3 claim 4 , and SEQ ID NO: 4.6. The set of primers of comprising primers having the polynucleotide sequence of SEQ ID NO: 53 claim 4 , SEQ ID NO: 2 claim 4 , SEQ ID NO: 54 claim 4 , and SEQ ID NO: 4.7. The set of primers of comprising primers having the polynucleotide sequence of SEQ ID NO: 5 claim 4 , SEQ ID NO: 6 claim 4 , SEQ ID NO: 7 claim 4 , and SEQ ID NO: 4.8. The set of primers of comprising primers having the polynucleotide sequence of SEQ ID NO: 8 claim 4 , SEQ ID NO: 9 claim 4 , SEQ ID NO: 1 claim 4 , and SEQ ID NO: 10.9. An in vitro method of obtaining a DNA copy of a segment of an HIV genome comprising:a. Obtaining an RNA copy of an HIV genome from a subject infected with HIV; i. SEQ ID NO: 1 and SEQ ID NO: 2,', 'ii. SEQ ID NO: 53 and SEQ ID NO: 2,', 'iii. SEQ ID NO: 5 and SEQ ID NO: 6, or', 'iv. SEQ ID NO: 8 and SEQ ID NO: 9; and, 'b. Reverse-transcribing the RNA with any one of the following primer pairs i. Subpart b(i) with primers SEQ ID NO: 3 and SEQ ID NO: 4,', 'ii. Subpart b(ii) with primers SEQ ID NO: ...

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04-04-2013 дата публикации

MODIFIED NUCLEOSIDES, ANALOGS THEREOF AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM

Номер: US20130084576A1
Принадлежит: Isis Pharmaceuticals, Inc.

The present invention provides modified nucleosides, analogs thereof and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides and analogs thereof that are useful for incorporation at the terminus of an oligomeric compound. Such oligomeric compounds can also be included in a double stranded composition. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. 158.-. (canceled)60. The compound of wherein Mis O.61. The compound of wherein J claim 60 , J claim 60 , Jand Jare each H.62. The compound of wherein Jforms a bridge with one of Jor J.64. The compound of wherein Qand Qare each H.66. The compound of wherein G is halogen claim 65 , OCH claim 65 , OCHF claim 65 , OCHF claim 65 , OCF claim 65 , OCHCH claim 65 , O(CH)F claim 65 , OCHCHF claim 65 , OCHCF claim 65 , OCH—CH═CH claim 65 , O(CH)—OCH claim 65 , O(CH)—SCH claim 65 , O(CH)—OCF claim 65 , O(CH)—N(R)(R) claim 65 , O(CH)—ONO(R)(R) claim 65 , O(CH)—O(CH)—N(R)(R) claim 65 , OCHC(═O)—N(R)(R) claim 65 , OCHC(═O)—N(R)—(CH)—NR)(R) or O(CH)—N(R)—C(═NR)[N(R)(R)] wherein R claim 65 , R claim 65 , Rand Rare each claim 65 , independently claim 65 , H or C-Calkyl.67. The compound of wherein said heterocyclic base moiety is a pyrimidine claim 66 , substituted pyrimidine claim 66 , purine or substituted purine.68. The compound of wherein said heterocyclic base moiety is uracil claim 67 , thymine claim 67 , cytosine claim 67 , 5-methylcytosine claim 67 , adenine or guanine.70. The oligomeric compound of wherein Mis O.71. The oligomeric compound of wherein J claim 70 , J claim 70 , Jand Jare each H.72. The oligomeric compound of wherein Jforms a bridge with one of Jor J.74. The oligomeric compound of wherein Qand Qare each H.76. The oligomeric compound of wherein Ris O and Rand Rare each claim 75 , independently claim 75 , OCH claim 75 , OCHCHor OCH(CH). ...

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11-04-2013 дата публикации

Fluorescent dyes

Номер: US20130089853A1
Автор: Praveen Pande, Zaiguo Li
Принадлежит: Enzo Life Sciences Inc

Provided are various compounds comprising the formula Also provided are fluorescent dyes comprising the above compound. Additionally, a fluorescence energy transfer system is provided that comprises the above-described fluorescent dye and a second dye, wherein the second dye is capable of energy transfer with the fluorescent dye. Further provided is a kit for labeling a target molecule, where the kit comprises the above-described fluorescent dye with additional reagents useful for labeling the target molecule. Additionally provided is a target molecule labeled with the above-described fluorescent dye. A method of labeling a target molecule is also provided. The method comprises contacting reactive group Z of the above-described fluorescent dye with the target molecule such that reactive group Z reacts with the target molecule to form a covalent bond between reactive group Z and the target molecule. Also, another method of labeling a target molecule is provided. The method comprises contacting the above-described fluorescent dye, which further comprises a member of a binding pair, with the target molecule, where the target molecule comprises a second member of the binding pair.

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11-04-2013 дата публикации

Compositions, methods and kits to detect adenovirus nucleic acids

Номер: US20130089859A1
Принадлежит: Gen Probe Prodesse Inc

The disclosed invention is related to methods, compositions, kits and isolated nucleic acid sequences for targeting Adenovirus nucleic acid. Compositions include amplification oligomers and/or detection probe oligomers. Kits and methods comprise at least one of these oligomers.

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11-04-2013 дата публикации

Process Using Dual Specificity Oligonucleotide and Dual Specificity Oligonucleotide

Номер: US20130090464A1
Автор: CHUN Jong-Yoon
Принадлежит: SEEGENE, INC.

The present invention relates to various processes by a template-dependent extension reaction using a dual specificity oligonucleotide and a dual specificity oligonucleotide composed of three different Tm portions therefor. Demonstrated in the present invention are the features of the dual specificity oligonucleotide, which are high hybridization specificity and mismatch tolerance. 1. A dual specificity oligonucleotide represented by the following general formula:{'br': None, 'sub': p', 'q', 'r, '5′-X—Y—Z-3′'}wherein,{'sub': p', 'm, 'Xrepresents a 5′-high Tspecificity portion having a hybridizing nucleotide sequence substantially complementary to a site on a template nucleic acid to hybridize therewith;'}{'sub': 'q', 'Yrepresents a separation portion comprising at least three contiguous universal bases;'}{'sub': r', 'm, 'Zrepresents a 3′-low Tspecificity portion having a hybridizing nucleotide sequence substantially complementary to a site on the template nucleic acid to hybridize therewith;'}p, q and r represent the number of nucleotides;p represents an integer of at least 15;q represents an integer of at least 3;r represents an integer of at least 3;X, Y, and Z are deoxyribonucleotide or ribonucleotide;{'sub': m', 'm', 'm, 'the Tof the 5′-high Tspecificity portion is higher at least 20° C. than that of the 3′-low Tspecificity portion;'}{'sub': 'm', 'the separation portion has the lowest Tin the three portions;'}{'sub': m', 'm, 'the 5′-high Tspecificity portion is longer than the 3′-low Tspecificity portion;'}{'sub': m', 'm', 'm', 'm, 'the separation portion forms a non base-pairing bubble structure under conditions that the 5′-high Tspecificity portion and the 3′-low Tspecificity portion are annealed to the template nucleic acid, enabling the 5′-high Tspecificity portion to separate from the 3′-low Tspecificity portion in terms of annealing specificity to the template nucleic acid,'}{'sub': m', 'm, 'whereby the annealing specificity of the dual specificity ...

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11-04-2013 дата публикации

ENA NUCLEIC ACID PHARMACEUTICALS CAPABLE OF MODIFYING SPLICING OF mRNA PRECURSORS

Номер: US20130090465A1
Принадлежит:

Oligonucleotides having a nucleotide sequence complementary to nucleotide numbers such as 2571-2607, 2578-2592, 2571-2592, 2573-2592, 2578-2596, 2578-2601 or 2575-2592 of the dystrophin cDNA (Gene Bank accession No. NM_004006.1) and therapeutic agents for muscular dystrophy comprising such oligonucleotides. 1. An oligonucleotide having the nucleotide sequence as shown in any one of SEQ ID NOS: 2-6, 10-13, 17, 19-22, 30-77, 87 or 88 in the SEQUENCE LISTING, or a pharmacologically acceptable salt thereof. The present application is a division of U.S. Ser. No. 12/847,237, filed Jul. 30, 2010, which is a division of U.S. Ser. No. 10/536,258, filed Dec. 13, 2005, which is a National Stage (371) of PCT/JP03/14915, filed Nov. 21, 2003, and claims priority to JP 2003-204381, filed Jul. 31, 2003, and JP 2002-340857, filed Nov. 25, 2002.The present invention relates to ENA nucleic acid pharmaceuticals capable of modifying splicing of mRNA precursors. More specifically, the present invention relates to antisense oligonucleotide compounds to splicing enhancer sequences within exon 19, 41, 45, 46, 44, 50, 55, 51 or 53 of the dystrophin gene, as well as therapeutic agents for muscular dystrophy comprising the compounds.Muscular dystrophy, which is a genetic muscular disease, is roughly classified into Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is the most frequently occurring genetic muscular disease and occurs at a ratio of 1 per 3,500 male births. DMD patients show symptoms of weakening of muscles in their childhood; thereafter, muscular atrophy progresses consistently and results in death at the age of around 20. Currently, there is no effective therapeutic for DMD. Development of therapeutics is strongly demanded by DMD patients throughout the world. BMD in many cases occurs in adulthood and most of the patients are capable of normal survival though slight weakening of muscles is observed. Mutations of deletions in the dystrophin gene have been ...

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18-04-2013 дата публикации

POLYANIONIC MULTIVALENT MACROMOLECULES FOR INTRACELLULAR TARGETING OF PROLIFERATION AND PROTEIN SYNTHESIS

Номер: US20130095035A1
Принадлежит: MIVENION GMBH

The present invention relates generally to methods and compositions for targeting of intracellular molecules involved in proliferation and protein synthesis of activated cells using polyanionic multivalent macromolecules. In particular aspect, multiple sulfate groups linked to polyol are specifically targeted to the cytoplasm and nucleus of proliferating and activated cells. The invention further comprises novel polyanionic macromolecular compounds and formulations. 1. Pharmaceutical composition comprising a sulfated polyglycerol and a therapeutic or diagnostic effector molecule that is covalently conjugated to said sulfated polyglycerol.2. Pharmaceutical composition according to of the formula P(OSOM)(L-G-E)with P is a polyol macromolecule wherein a number n of hydroxyl groups is substituted by sulfate groups OSOM claim 1 , M is a cationic inorganic or organic counter ion to the anionic sulfate group claim 1 , E is therapeutic or diagnostic effector molecule claim 1 , L is a linker or spacer between P and E claim 1 , G is a reactive group for the covalent attachment between L and E claim 1 , and m is a number of 1-100.3. Pharmaceutical composition according to for treating a disease by intracellular uptake of said sulfated polyglycerol and a therapeutic or diagnostic effector molecule into activated cells or proliferative cells and by inhibiting NF-kappaB and/or AP-1 and/or inhibiting TGF-beta synthesis in said cells.4. Conjugate comprising a sulfated polyglycerol and a therapeutic or diagnostic effector molecule that is covalently conjugated to said sulfated polyglycerol.5. Conjugate according to of the formula P(OSOM)(L-G-E)with P is a polyol macromolecule wherein a number n of hydroxyl groups is substituted by sulfate groups OSOM claim 4 , M is a cationic inorganic or organic counter ion to the anionic sulfate group claim 4 , E is therapeutic or diagnostic effector molecule claim 4 , L is a linker or spacer between P and E claim 4 , G is a reactive group for the ...

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18-04-2013 дата публикации

THERAPEUTIC USES OF INHIBITORS OF RTP801

Номер: US20130095117A1
Принадлежит:

The present invention provides novel molecules, compositions, methods and uses for treating microvascular disorders, eye diseases and respiratory conditions based upon inhibition of the RTP801 gene and/or protein. 128-. (canceled)29. A double-stranded compound comprising a sense strand and an antisense strand wherein the sense strand comprises ribonucleotides , the sequence of which is set forth in SEQ ID NO:16 and the antisense strand comprises ribonucleotides , the sequence of which is set forth in SEQ ID NO:66;wherein each ribonucleotide in the sense strand and in the antisense strand is independently unmodified or modified; andwherein each ribonucleotide is bound to each adjacent ribonucleotide by a covalent bond.31. The compound of claim 30 , wherein at least one A claim 30 , C claim 30 , G claim 30 , or U is a sugar-modified ribonucleotide.32. The compound of claim 31 , wherein in the sugar-modified ribonucleotide a 2′ OH group is replaced by —H claim 31 , —OCH claim 31 , —OCHCH claim 31 , —OCHCHCHor —NH.33. The compound of claim 32 , wherein the 2′OH group is replaced by —OCH).34. The compound of claim 30 , wherein at least one A claim 30 , C claim 30 , G or U is a ribonucleotide modified in its base.35. The compound of claim 29 , wherein at least one covalent bond comprises a phosphorothioate bond.36. A method of treating a patient suffering from a disorder associated with elevated expression of RTP801 which comprises administering to the patient the compound of in an amount effective to reduce the expression of RTP801 so as to thereby treat the patient.37. The method of claim 36 , wherein the disorder is a respiratory disorder claim 36 , an eye disease claim 36 , a microvascular disorder claim 36 , or a spinal cord injury.39. The compound of claim 38 , wherein x=y=19.40. The compound of claim 38 , wherein at least one A claim 38 , C claim 38 , G claim 38 , or U comprises a sugar-modified ribonucleotide.41. The compound of claim 40 , wherein in the sugar- ...

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18-04-2013 дата публикации

MODULATION OF INSULIN LIKE GROWTH FACTOR I RECEPTOR EXPRESSION

Номер: US20130096176A1
Принадлежит: Antisense Therapeutics Limited

The present invention provides compositions and methods for modulating the expression of growth factor gene. In particular, this invention relates to compounds, particularly oligonucleotide compounds, which, in preferred embodiments, hybridize with nucleic acid molecules encoding the Insulin Like Growth Factor I receptor (IGF-I receptor or IGF-IR) and in particular human IGF-IR. Such compounds are exemplified herein to modulate proliferation which is relevant to the treatment of proliferative and inflammatory skin disorders and cancer. It will be understood, however, that the compounds can be used for any other condition in which the IGF-IR is involved including inflammatory condition. 144-. (canceled)45. An antisense oligonucleotide comprising 20 to 80 nucleobases in length targeted to a nucleic acid molecule encoding human insulin-like growth factor receptor (IGF-IR) , wherein said oligonucleotide specifically hybridizes with said nucleic acid molecule and inhibits the expression of IGF-IR and wherein said oligonucleotide comprises a deoxynucleotide region flanked on both the 5′ and the 3′ ends of said deoxynucleotide region with 2′-O-(2-methoxyethyl) nucleotides.46. The oligonucleotide as claimed in claim 45 , wherein the oligonucleotide is 20 to 30 nucleobases in length.47. The oligonucleotide as claimed in claim 45 , wherein the oligonucleotide is 8 to 30 nucleobases in length.48. The oligonucleotide as claimed in claim 45 , wherein said oligonucleotide comprises a ten deoxynucleotide region flanked on both the 5′ and the 3′ ends of said ten deoxynucleotide region with five 2′-O-(2-methoxyethyl) nucleotides.49. The oligonucleotide of which is a DNA oligonucleotide claim 45 , an RNA oligonucleotide or a chimeric oligonucleotide.50. The oligonucleotide of claim 45 , wherein the nucleic acid molecule is an RNA molecule encoding human insulin-like growth factor receptor.51. The oligonucleotide of claim 50 , wherein at least a portion of said oligonucleotide ...

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25-04-2013 дата публикации

Particle matrix for storage of biomolecules

Номер: US20130101981A1
Принадлежит: Individual

Matrices for manipulation of biopolymers, including the separation, purification, immobilization and archival storage of biopolymers is disclosed.

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25-04-2013 дата публикации

RNA APTAMERS AGAINST BAFF-R AS CELL-TYPE SPECIFIC DELIVERY AGENTS AND METHODS FOR THEIR USE

Номер: US20130102654A1
Принадлежит: CITY OF HOPE

In one embodiment, a B cell specific aptamer-siRNA chimera is provided. The B cell specific aptamer-siRNa chimera may include an RNA aptamer that binds BAFF-R and an siRNA molecule conjugated to the RNA aptamer via a nucleotide linker. In another embodiment, a B cell specific RNA aptamer is provided. The RNA aptamer may be a molecule that binds to BAFF-R that has the sequence SEQ ID NO:37, SEQ ID NO:38 or SEQ ID NO:39. In some embodiments, the RNA aptamer is conjugated, via a nucleotide linker, to an siRNA molecule that suppresses expression of one or more target oncogenes in one or more B cells. In one aspect, the one or more target oncogenes are selected from Bcl6, Bcl2, STAT3, Cyclin D1, Cyclin E2 and c-myc. In another embodiment, methods for treating a B cell malignancy in a cancer patient are provided. Such methods may include administering a therapeutically effective amount of a therapeutic composition, the therapeutic composition comprising a B cell specific RNA aptamer that binds BAFF-R. 1. A B cell specific aptamer-siRNA chimera comprising:an RNA aptamer that binds BAFF-R, andan siRNA molecule conjugated to the RNA aptamer via a nucleotide linker.2. The aptamer-siRNA chimera of claim 1 , wherein the RNA aptamer is an RNA molecule having the sequence SEQ ID NO:37 claim 1 , SEQ ID NO:38 or SEQ ID NO:39.3. The aptamer-siRNA chimera of claim 1 , wherein the aptamer claim 1 , upon binding BAFF-R claim 1 , blocks BAFF ligand mediated cell proliferation.4. The aptamer-siRNA chimera of claim 1 , wherein the siRNA molecule suppresses expression of a target oncogene when internalized by a B cell.5. The aptamer-siRNA chimera of claim 4 , wherein the target oncogene is selected from Bcl6 claim 4 , Bcl2 claim 4 , STAT3 claim 4 , Cyclin D1 claim 4 , Cyclin E2 and c-myc.6. The aptamer-siRNA chimera of claim 1 , wherein the siRNA molecule comprises a sense strand SEQ ID NO:7 and an antisense strand SEQ ID NO:8.7. The aptamer-siRNA chimera of claim 1 , wherein the siRNA ...

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25-04-2013 дата публикации

ALKYNYL-DERIVATIZED CAP ANALOGS, PREPARATION AND USES THEREOF

Номер: US20130102655A1
Принадлежит: LIFE TECHNOLOGIES CORPORATION

Alkynyl-derivatized cap analogs, alkynyl-modified capped RNA, 1,4-disubstituted triazole-derivatized capped RNA, methods of preparation, methods of isolation, and uses thereof are provided. The “click” modification facilitates detection and isolation of capped RNAs and the 1,4-disubstituted triazole derivatives formed by the “click” reaction are useful for producing RNA transcripts and encoded protein. 1. A composition comprising an alkynyl-derivatized cap analog having the structure:{'sub': '3', 'sup': '7,3′-O-alkynyl', 'RG[5′]p[p]np[5′]G,'}{'sub': '3', 'sup': '7,3′-O-alkynyl', 'RG[5′]p[p]np[5′]A,'}{'sub': '3', 'sup': '7,2′-O-alkynyl', 'b': '5', 'RG[′]p[p]np[5′]G,'}{'sub': '3', 'sup': '7,2′-O-alkynyl', 'b': '5', 'RG[′]p[p]np[5′]A,'} [{'sub': '3', 'Ris alkyl or arylalkyl,'}, 'the alkynyl moiety comprises 3-24 carbon atoms, a terminal alkyne, and is optionally substituted,', 'n is 1, 2, or 3,', 'A is adenosine, and', 'G is guanosine., 'wherein'}, 'or a salt thereof,'}2. A composition comprising RNA having a cap analog of covalently bonded thereto.4. The composition of claim 3 , wherein Rcomprises O(CH)C≡CH and m is 1 to 6 claim 3 , and Rcomprises OH.5. The composition of claim 3 , wherein Rcomprises O(CH)C≡CH and m is 1 to 6 claim 3 , and Rcomprises OH.6. The composition of claim 4 , wherein m is 1.7. The composition of wherein the alkyl is methyl claim 3 , ethyl claim 3 , propyl claim 3 , isopropyl claim 3 , butyl or isobutyl.8. The composition of attached to the 5′ end of an RNA molecule.9. The composition of wherein the RNA molecule is a mRNA molecule.10. A method of producing alkynyl-modified capped RNA comprising: contacting a nucleic acid substrate with a RNA polymerase and the alkynyl-derivatized cap analog of in the presence of nucleotide triphosphates under conditions and for a time to produce alkynyl-modified capped RNA.11. The method of further comprising contacting the alkynyl-modified capped RNA with an azide-derivatized moiety to form a 1 claim 10 ,4- ...

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25-04-2013 дата публикации

NUCLEIC ACID SEQUENCES ENCODING STRICTOSIDINE SYNTHASE PROTEINS

Номер: US20130102767A1
Принадлежит:

Isolated polynucleotides and polypeptides encoded thereby are described, together with the use of those products for making transgenic plants. 1. An isolated nucleic acid comprising a polypeptide coding sequence having at least 99 percent identity to SEQ ID NO:2. This application is a continuation-in-part of U.S. patent application Ser. No. 13/157,066, filed Jun. 9, 2011, which is a continuation-in-part of U.S. patent application Ser. No. 12/639,295, filed Dec. 16, 2009 (now U.S. Pat. No. 7,989,609), which is a continuation-in-part of U.S. patent application Ser. No. 12/040,538, filed Feb. 29, 2008 (now U.S. Pat. No. 7,659,386), which is a continuation-in-part of U.S. patent application Ser. No. 11/368,321, filed Mar. 3, 2006 (now U.S. Pat. No. 7,365,183), which is a continuation-in-part of U.S. patent application Ser. No. 11/006,231, filed Dec. 6, 2004, which is a continuation of U.S. patent application Ser. No. 10/645,822, filed Aug. 22, 2003, which is a continuation-in-part of the following U.S. Patent Applications: (a) U.S. patent application Ser. No. 10/336,798, filed Jan. 6, 2003, which is a continuation of U.S. patent application Ser. No. 10/136,365, filed May 2, 2002, which claims priority to U.S. patent application Ser. No. 09/731,809, filed Dec. 8, 2000, which claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 60/169,691, filed Dec. 8, 1999, (b) U.S. patent application Ser. No. 09/513,996, filed Feb. 25, 2000, which is a continuation-in-part of and claims priority to U.S. Provisional Patent Application No. 60/169,691, filed Dec. 8, 1999, and (c) U.S. patent application Ser. No. 10/461,476, filed Jun. 16, 2003, which is a continuation of U.S. patent application Ser. No. 10/191,406, filed Jul. 10, 2002, which is a continuation of U.S. patent application Ser. No. 09/940,255, filed Aug. 24, 2001. The entire contents of these related applications are incorporated by reference in their entirety. This application claims priority to ...

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02-05-2013 дата публикации

Procedure for the specific isolation of total dna content of bacterial germs and a kit for this purpose

Номер: US20130109027A1
Принадлежит: DIAGON KFT

Procedure for the specific isolation of total DNA content of bacterial germs of different samples, in the course of which the cells are lysated, the DNA content of the lysate is bound selectively, it is washed and then the desalinated linear polymer nucleic acid is eluted from the binding surface in an aqueous solution. Before cell lysis the nonviable bacterial cells are separated from the viable cells on the basis of their different cell surface physical-chemical characteristics, the viable cells of the sample are kept and then lysated using a mechanical and/or enzymatic, favourably lysozyme enzymatic method. After this exclusively double-stranded DNA deriving from the lysate of viable cells is bound on a —SiO 2 —TiO 2- matrix containing chemically activated —OH and dodecylamine groups, and after washing it, the desalinated linear polymer nucleic acid is eluted in an aqueous solution.

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02-05-2013 дата публикации

Microrna compositions and methods related thereto

Номер: US20130109628A1
Принадлежит: EMORY UNIVERSITY

The disclosure relates to microRNAs (miRNAs) for the prophylaxis and/or treatment of neoplasia. The disclosure relates in particular to sequence corresponding to miR2 and the miR-548 family, including precursors, mature forms, fragments, and combinations thereof for the prophylaxis and/or treatment of neoplasias, particularly lung, stomach, and cervical cancer, alone or in combination with additional cancer treatments and therapeutics.

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02-05-2013 дата публикации

PROPHYLACTIC OR THERAPEUTIC AGENT FOR DIABETES

Номер: US20130109744A1
Принадлежит:

The present invention provides a prophylactic or therapeutic drug for diabetes, which contains a polynucleotide such as miR-199b* and the like. Moreover, the present invention provides a method for screening for a prophylactic or therapeutic drug for diabetes, which includes measuring an expression level of a polynucleotide such as miR-199b* and the like. Furthermore, the present invention provides a method for determining the susceptibility to a prophylactic or therapeutic drug for diabetes, which includes measuring an expression level of a polynucleotide such as miR-199b* and the like. 1. An agent for the prophylaxis or treatment of diabetes , comprising a polynucleotide comprising a base sequence the same as or having a homology of not less than 90% to the base sequence shown by SEQ ID NO: 1 , 2 , 3 or 4 or a polynucleotide comprising a base sequence complementary to the base sequence , or a salt thereof.2. An agent for proliferating pancreatic β cells , comprising a polynucleotide comprising a base sequence the same as or having a homology of not less than 90% to the base sequence shown by SEQ ID NO: 1 , 2 , 3 or 4 or a polynucleotide comprising a base sequence complementary to the base sequence , or a salt thereof.3. A method for the prophylaxis or treatment of diabetes in a mammal , comprising administering an effective amount of a polynucleotide comprising a base sequence the same as or having a homology of not less than 90% to the base sequence shown by SEQ ID NO: 1 , 2 , 3 or 4 or a polynucleotide comprising a base sequence complementary to the base sequence , or a salt thereof , to said mammal.4. A method for proliferating pancreatic β cells in a mammal , comprising administering an effective amount of a polynucleotide comprising a base sequence the same as or having a homology of not less than 90% to the base sequence shown by SEQ ID NO: 1 , 2 , 3 or 4 or a polynucleotide comprising a base sequence complementary to the base sequence , or a salt thereof , ...

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02-05-2013 дата публикации

Detection or quantification of desirable target molecules, novel dyes, composite dyes, and oligonucleotides or polynucleotides comprising such dyes

Номер: US20130109847A1

The present invention provides dyes, reactive dyes and labeled reagents that may be used in the detection or quantification of desirable target molecules, such as proteins and nucleic acids. Dyes are provided that may be used free in solution where the binding of the dye to the target molecule provides signal generation. Dyes are also provided that comprise reactive groups that may be used to attach the dyes to probes that will bind to desirable target molecules. The novel dyes of the present invention have been modified by the addition of charged and polar groups to provide beneficial properties. 2. The dye of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , or Rfurther comprises a reactive group.3. The dye of claim 2 , wherein said reactive group comprises a nucleophilic reactive group claim 2 , an electrophilic reactive group claim 2 , a terminal alkene claim 2 , a terminal alkyne claim 2 , a coordinate group or an alkylating agent.4. The dye of claim 3 , wherein said nucleophilic reactive group comprises a thiol claim 3 , amine or hydroxyl group.5. The dye of claim 3 , wherein said electrophilic reactive group comprises an isocyanate claim 3 , isothiocyanate claim 3 , monochlorotriazine claim 3 , dichlorotriazine claim 3 , 4 claim 3 ,6 claim 3 ,-dichloro-1 claim 3 ,3 claim 3 ,5-triazines claim 3 , mono- or di-halogen substituted pyridine claim 3 , mono- or di-halogen substituted diazine claim 3 , maleimide claim 3 , haloacetamide claim 3 , aziridine claim 3 , sulfonyl halide claim 3 , acid halide claim 3 , hydroxysuccinimide ester claim 3 , hydroxysulfosuccinimide ester claim 3 , imido ester claim 3 , hydrazine claim 3 , azidonitrophenol claim 3 , azide claim 3 , 3-(2-pyridyl dithio)-proprionamide claim 3 , glyoxal or aldehyde group.6. The dye of claim 1 , wherein said dye further comprises one or more charged groups or polar groups.7. ...

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02-05-2013 дата публикации

Multidimensional Supramolecular Structures Essentially Made of Assembled I-Motif Tetramers

Номер: US20130109848A1

The present invention pertains to a supramolecular structure based on i-motif tetramers of C—X—Coligonucleotides, wherein m and n are integers comprised between 2 and 9, and X is a linker such as A, T, G, a modified deoxynucleotide or a diol spacer. These supramolecular structures can be dissociated, when necessary, by a mere pH change. The present invention also relates to methods for obtaining such a supramolecular structure. 1. (canceled)2. A supramolecular structure comprising N C—X—C(SEQ ID No: 1) oligonucleotides , wherein m and n are integers comprised between 2 and 7 , preferably between 3 and 7 , X is selected in the group consisting of A , T , G , a modified deoxynucleotide and a diol spacer , N an integer ≧8 and wherein each oligonucleotide is part of an i-motif tetramer.3. The supramolecular structure of claim 2 , wherein m≠n.4. The supramolecular structure of claim 2 , wherein (m claim 2 , n) is selected in the group of (4 claim 2 , 7) and (7 claim 2 , 4).5. The supramolecular structure according to claim 2 , wherein X=G.6. The supramolecular structure according to claim 2 , which comprises oligonucleotides having different sequences.7. The supramolecular structure according to claim 6 , comprising oligonucleotides of sequence C—X—C(SEQ ID No: 1) and terminator oligonucleotides.8. The supramolecular structure according to claim 7 , wherein at least part of said terminator oligonucleotides are covalently linked to a reactive group.9. The supramolecular structure according to claim 2 , wherein N≧50.10. A process for producing a supramolecular structure according to claim 2 , wherein said process comprises the following steps:{'sub': m', 'n, '(i) incubating a solution of oligonucleotides of sequence C—X—C(SEQ ID No: 1) wherein n and m are integers comprised between 2 and 9, preferably between 3 and 7, and X is selected in the group consisting of A, T, G, a modified deoxynucleotide and a diol spacer, in a buffer having a pH in the range 3 to 6, and'}(ii) ...

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02-05-2013 дата публикации

RNA Containing Modified Nucleosides and Methods of Use Thereof

Номер: US20130111615A1
Принадлежит:

This invention provides RNA, oligoribonucleotide, and polyribonucleotide molecules comprising pseudouridine or a modified nucleoside, gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of RNA, oligoribonucleotide, and polyribonucleotide molecules. 178-. (canceled)79. A composition comprising an in vitro-synthesized modified RNA encoding a protein of interest for translation in a mammalian cell , wherein said in vitro-synthesized modified RNA comprises the modified nucleoside pseudouridine.80. The composition of claim 79 , wherein said in vitro-synthesized modified RNA further comprises a 5′-terminal cap comprising N-methylguanine and a poly-A tail.81. The composition of claim 80 , wherein the cap in the in vitro-synthesized modified RNA comprises mGpppG cap or 3′-O-methyl-mGpppG cap.82. The composition of claim 79 , wherein said in vitro-synthesized modified RNA further comprises a cap-independent translational enhancer.83. The composition of claim 79 , wherein said in vitro-synthesized modified RNA further comprises 5′ and 3′ untranslated regions (UTRs) that enhance translation.84. The composition of claim 83 , wherein said 5′ and 3′ UTRs comprise at least one UTR selected from the group consisting of a beta-globin 5′ UTR claim 83 , a tobacco etch virus (TEV) 5′ UTR claim 83 , and a beta-globin 3′ UTR.85. The composition of claim 79 , wherein said composition is present in a mammalian cell that is in culture claim 79 , in a tissue claim 79 , or in vivo in a mammal.86. The method of claim 85 , wherein the mammalian cell is a cell selected from the group consisting of an antigen-presenting cell claim 85 , a dendritic cell claim 85 , a macrophage claim 85 , a neural cell claim 85 , a brain cell claim 85 , an ...

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09-05-2013 дата публикации

METHOD FOR INHIBITING CANCER STEM CELL LIKE PROPERTIES AND CHEMORADIORESISTANT PROPERTIES OF CANCER OR TUMOR CELLS WITH MICRORNA145

Номер: US20130115299A1
Принадлежит: Taipei Veterans General Hospital

The present invention provides a method for inhibiting cancer stem cell like properties and chemoradioresistant properties of cancer or tumor cells comprising delivering miR145 to the cancer or tumor cells, particularly brain tumor and head and neck cancer cells. The invention further provides a pharmaceutical composition comprising miR145 and a method for treating brain tumor and/or head and neck cancer comprising administration of miR145 to a subject in need thereof. 1. A method for inhibiting cancer stem cell-like and chemoradioresistant properties of cancer or tumor cells comprising delivering miR145 to the cancer or tumor cells.2. The method of claim 1 , wherein the tumor cells are brain tumor cells.3. The method of claim 2 , wherein the brain tumor is malignant glioma.4. The method of claim 1 , wherein the cancer cells are head and neck cancer (HNC) cells.5. The method of claim 4 , wherein the head and neck cancer is head and neck squamous cell carcinoma.6. The method of claim 1 , wherein the miR145 is encapsulated in a polymer as a delivery vehicle.7. The method of claim 6 , the polymer is a polyurethane (PU).8. The method of claim 7 , the polyurethane is a synthesized polyurethane (PU) with short branch polyetherimide (sbPEI).9. A pharmaceutical composition for inhibiting cancer stem cell-like and chemoradioresistant properties of cancer or tumor cells comprising miR145.10. The pharmaceutical composition of claim 9 , wherein the miR145 is encapsulated in a PU-sbPEI11. The pharmaceutical composition of claim 10 , which is used for treating brain tumor.12. The pharmaceutical composition of claim 11 , wherein the brain tumor is malignant glioma.13. The pharmaceutical composition of claim 9 , which is used for treating HNC.14. The pharmaceutical composition of claim 13 , wherein the HNC is head and neck squamous cell carcinoma15. The pharmaceutical composition of claim 9 , which further comprises a pharmaceutically acceptable carrier.16. A method for treating ...

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09-05-2013 дата публикации

Methods for the Development of Vaccines Based on Oligosaccharide-Oligonucleotide Conjugates

Номер: US20130116417A1
Принадлежит: BRANDEIS UNIVERSITY

Described herein are oligosaccharide-oligonucleotide conjugates useful as vaccines against one or more human or veterinary therapeutic indications, and methods of synthesizing and identifying them. The conjugates may be identified using non-human antibodies as binding targets, thereby expanding the power and scope of the invention. Efficacious conjugates may be identified through an iterative. 1. A method , comprising the steps of: wherein', 'the oligonucleotide comprises a first primer binding site on the 5′ end, a randomized region, and a stem-loop region;', 'the randomized region is located between the first primer binding site and the stem-loop region;', 'the stem-loop region comprises a second primer binding site; and', 'at least one of the deoxyribonucleotide triphosphates comprises a reactive substituent;, '(a) combining an oligonucleotide, a first DNA polymerase, and a plurality of deoxyribonucleotide triphosphates,'}thereby forming an extended oligonucleotide comprising an original strand and an extended strand, wherein the extended strand comprises at least one reactive substituent;(b) combining a plurality of modifying compounds and the extended oligonucleotide under reaction conditions,thereby forming a modified extended oligonucleotide comprising the original strand and a modified extended strand; and(c) combining a primer complementary to the second primer binding site, a second DNA polymerase, the modified extended oligonucleotide, and a plurality of deoxyribonucleotide triphosphatesthereby creating a duplex with the original strand and displacing the modified extended strand.2. (canceled)3. The method of claim 1 , wherein oligonucleotide is in the form of a partial stem-loop.45-. (canceled)6. The method of claim 1 , wherein the deoxyribonucleotide triphosphate comprising a reactive substituent is an unnatural deoxyribonucleotide triphosphate.7. The method of claim 1 , wherein the reactive substituent is ethynyl.8. The method of claim 1 , wherein the ...

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09-05-2013 дата публикации

POST-SYNTHETIC CHEMICAL MODIFICATION OF RNA AT THE 2'-POSITION OF THE RIBOSE RING VIA "CLICK" CHEMISTRY

Номер: US20130116419A1
Принадлежит:

This invention relates to the post-synthetic chemical modification of RNA at the 2′-position on the ribose ring via a copper catalyzed Huisgen cycloaddition (“click” chemistry: Kolb, Sharpless Drug Discovery Today 2003, 8, 1128). The invention 1) avoids complex, tedious multi-step syntheses of each desired modified ribonucleoside; 2) allows diverse chemical modifications using high-fidelity chemistry that is completely orthogonal to commonly used alkylamino, carboxylate and disulfide linker reactivities; 3) allows introduction of functional groups that are incompatible with modern automated solid-phase synthesis of RNA and subsequent cleavage-deprotection steps; 4) allows introduction of functional groups useful as targeting ligands; and 5) enables high-throughput structure-activity relationship studies on chemically modified RNA in 96-well format. 1. A process for introducing 2′-modifications into RNA , said process comprises a) obtaining RNA with an alkyne functional group at the 2′-position on at least one ribose ring; b) creating a solution of RNA in a solvent; and c) adding an organic azide and a metal catalyst to the solution to form a reaction and creating a 2′-modified RNA.2. The process of claim 1 , wherein the process is conducted in high-throughput format.3. The process of claim 1 , wherein the solvent of step (b) is selected from the group consisting of an aqueous buffer solution claim 1 , aqueous DMSO claim 1 , CHCN claim 1 , DMF claim 1 , DMAc claim 1 , NMP and a suitable ionic liquid.4. The process of claim 1 , wherein the metal catalyst of step (c) is selected from copper and ruthenium.5. The process of claim 4 , wherein the metal catalyst of step (c) is Cu(I) and a suitable ligand to stabilize the Cu(I) oxidation state.6. The process of claim 1 , wherein step (c) is performed at a temperature of between −20° C. to 300° C.7. The process of claim 6 , wherein step (c) is performed at a temperature of between 20° C. to 100° C. for 0.5 to 18 hours.8. The ...

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09-05-2013 дата публикации

5' MODIFIED NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM

Номер: US20130116420A1
Принадлежит: Isis Pharmaceuticals, Inc.

The present invention provides 5′ modified nucleosides and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides having at least one 5′-substituent and an optional 2′ substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. 146-. (canceled)48. The 5′ modified nucleoside of wherein Bx is uracil claim 47 , thymine claim 47 , cytosine claim 47 , 5-methylcytosine claim 47 , adenine or guanine.49. The 5′ modified nucleoside of wherein qand qare each claim 48 , independently claim 48 , OCH claim 48 , OCHCHor OC(H)(CH)and qis O.50. The 5′ modified nucleoside of wherein r is 1 claim 49 , Mis H and Mis hydroxyl or r is 0 claim 49 , Mis O(CH)CN and Mis N[CH(CH)].51. The 5′ modified nucleoside of wherein G is halogen claim 50 , OCH claim 50 , OCHF claim 50 , OCHF claim 50 , OCF claim 50 , OCHCH claim 50 , O(CH)F claim 50 , OCHCHF claim 50 , OCHCF claim 50 , OCH—CH═CH claim 50 , O(CH)—OCH claim 50 , O(CH)—SCH claim 50 , O(CH)—OCF claim 50 , O(CH)—N(R)(R) claim 50 , O(CH)—ON(R)(R) claim 50 , O(CH)—O(CH)—N(R)(R) claim 50 , OCHC(═O)—N(R)(R) claim 50 , OCHC(═O)—N(R)—(CH)—N(R)(R) or O(CH)—N(R)—C(═NR)[N(R)(R)] wherein R claim 50 , R claim 50 , Rand Rare each claim 50 , independently claim 50 , H or C-Calkyl.52. The 5′ modified nucleoside of wherein G is F claim 51 , OCH claim 51 , O(CH)—OCH claim 51 , OCHC(═O)—N(H)CHor OCHC(═O)—N(H)—(CH)—N(CH).53. The 5′ modified nucleoside of wherein g is 1.54. The 5′ modified nucleoside of wherein three of q claim 53 , q claim 53 , qand qare each H.55. The 5′ modified nucleoside of wherein one of qand qis H claim 53 , one of qand qis H and the other two of q claim 53 , q claim 53 , qand qare other than H.56. The 5′ modified nucleoside of wherein ...

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16-05-2013 дата публикации

Nucleic Acid of Formula (I): GlXmGn, or (II): ClXmCn, in Particular as an Immune-Stimulating Agent/Adjuvant

Номер: US20130121988A1
Принадлежит: CureVac AG

The present invention relates to a nucleic acid of the general formula (I): G l X m G n , which may be modified by a lipid. The invention relates further to a pharmaceutical composition containing an immune-stimulating agent according to the invention in combination with a pharmaceutically active carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). The present invention can relate to a vaccine, which corresponds to a pharmaceutical composition of the invention, wherein the pharmaceutically active component induces a specific immune response (e.g. an antigen). The present invention can relate to the use of a nucleic acid of the invention or a pharmaceutical composition according to the invention for the treatment of infectious diseases, autoimmune disease, allergies or cancer diseases.

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16-05-2013 дата публикации

Nucleic Acid Amplification Using A Reversibly Modified Oligonucleotide

Номер: US20130122507A1
Автор: Bi Wanli
Принадлежит:

The present invention provides a method for amplification of a target nucleic acid sequence or signal, wherein an amplification reaction mixture is used which contains at least one reversibly modified oligonucleotide having a non-hydroxyl group 3′ end which can be converted into a hydroxyl 3′ end upon exposure to a chemical and/or irradiation and/or a range of temperature. The present invention also provides a reversibly modified oligonucleotide as described above, and a nucleic acid amplification reaction mixture and kit comprising such an oligonucleotide. 143.-. (canceled)44. A method for regenerating a 3′ hydroxyl group , the method comprising:using a mixture comprising at least one reversibly modified oligonucleotide having a non-hydroxyl group 3′ end which can be converted into a 3′ hydroxyl group, wherein the oligonucleotide has a carboxylic acid ester group at its 3′ end;exposing the mixture to a first chemical and a first range of temperature, wherein the first chemical and the first range of temperatures regenerate the 3′ hydroxyl group, wherein the first chemical is an amine; andregenerating the 3′ hydroxyl group of the at least one reversibly modified oligonucleotide having a non-hydroxyl 3′ end.45. The method of claim 44 , wherein the amine is selected from the group consisting of methylamine claim 44 , ethylenediamine claim 44 , and triethylamine.46. The method of claim 45 , wherein the amine is methylamine.47. The method of claim 45 , wherein the amine is ethylenediamine.48. The method of claim 45 , wherein the amine is triethylamine.49. The method of claim 44 , wherein the carboxylic acid ester is maleic acid ester claim 44 , and the first chemical is methylamine.50. The method of claim 44 , wherein the carboxylic acid ester is maleic acid ester claim 44 , and the first chemical is ethylenediamine.51. The method of claim 44 , wherein the carboxylic acid ester is maleic acid ester claim 44 , and the first chemical is triethylamine.52. The method of ...

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16-05-2013 дата публикации

NOVEL SIRNA STRUCTURES

Номер: US20130123334A1
Принадлежит:

The invention relates to siRNA compounds possessing novel sequences and structural motifs which down-regulate the expression of specific human genes. The invention also relates to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The present invention also provides a method of treating and/or preventing the incidence or severity of various diseases or conditions associated with the genes and/or symptoms associated with such diseases or conditions comprising administering to a subject in need of treatment for such disease or condition and/or symptom the compound or the pharmaceutical composition in a therapeutically effective dose so as to thereby treat the subject. 2. The compound according to claim 1 , wherein x=y=19.3. (canceled)4. (canceled)5. The compound according to claim 2 , wherein the at least one unconventional moiety is a mirror nucleotide.6. The compound according to claim 5 , wherein the mirror nucleotide is present at position 17 claim 5 , position 18 or positions 17 and 18.78.-. (canceled)9. The compound according to claim 40 , wherein (N)x comprises nine alternating modified ribonucleotides.10. The compound according to claim 40 , wherein z″ is present.11. (canceled)13. The compound according to claim 12 , wherein x=y=19.1434-. (canceled)35. The compound according claim 47 , wherein the oligonucleotide sequences of (N)x and (N′)y comprise any one of the sequence pairs set forth in SEQ ID NOS: 229 and 230; 231-232; 233-234; 235-236; 237-238; 239-240; 241-242; 243-244; 245-246; 247-248; 249-250; 251-252; 253-254; or 255-256.36. A pharmaceutical composition comprising the compound according to ; and a pharmaceutically acceptable carrier.37. A method for treating or preventing the incidence or severity of a disease or condition in a subject in need thereof wherein the disease or condition and/or symptoms associated therewith is selected from the group consisting of claim 36 , glaucoma claim 36 , ocular ...

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16-05-2013 дата публикации

METHODS AND COMPOSITIONS FOR THE SPECIFIC INHIBITION OF KRAS BY ASYMMETRIC DOUBLE-STRANDED RNA

Номер: US20130123342A1
Автор: Brown Bob D.
Принадлежит: Dicerna Pharmaceuticals, Inc.

This invention relates to compounds, compositions, and methods useful for reducing KRAS target RNA and protein levels via use of Dicer substrate siRNA (DsiRNA) agents possessing asymmetric end structures. 1. An isolated double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands and a duplex region of at least 25 base pairs , wherein each of said first and second nucleic acid strands comprises RNA and has a length which is at least 25 and at most 35 nucleotides , wherein said second oligonucleotide strand is sufficiently complementary to SEQ ID NO: 164 or SEQ ID NO: 4938 along at least 19 nucleotides of said second oligonucleotide strand length to reduce KRAS target gene expression when said double stranded nucleic acid is introduced into a mammalian cell.2. The isolated dsNA of claim 1 , wherein starting from the first nucleotide (position 1) at the 3′ terminus of the first oligonucleotide strand claim 1 , position 1 claim 1 , 2 and/or 3 is substituted with a modified nucleotide.3. The isolated dsNA of claim 1 , wherein said 3′ terminus of said first strand and said 5′ terminus of said second strand form a blunt end.4. The isolated dsNA of claim 1 , wherein said first strand is 25 nucleotides in length and said second strand is 27 nucleotides in length.5. The isolated dsNA of claim 1 , wherein said second strand comprises a sequence selected from the group consisting of SEQ ID NO: 29 and SEQ ID NO: 4452.6. The isolated dsNA of claim 1 , wherein said first strand comprises a sequence selected from the group consisting of SEQ ID NO: 108 and SEQ ID NO: 4695.7. The isolated dsNA of comprising a first strand sequence comprising SEQ ID NO: 108 and a second strand sequence comprising SEQ ID NO: 29.8. The isolated dsNA of comprising a first strand sequence comprising SEQ ID NO: 4695 and a second strand sequence comprising SEQ ID NO: 4452.9. The isolated dsNA of claim 2 , wherein said modified nucleotide residue of said 3′ terminus of said first ...

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16-05-2013 дата публикации

NUCLEIC ACID MOLECULE CAPABLE OF BINDING TO c-MET AND USE THEREOF

Номер: US20130123350A1
Принадлежит:

The present invention provides a nucleic acid molecule capable of binding to c-Met as a substance that can be used for clarification of the pathogenic mechanism of diseases caused by c-Met, diagnosis and treatment of the diseases, and the like, and also the use thereof. The c-Met binding nucleic acid molecule of the present invention is any one of the following nucleic acid molecules (A1), (A2), (B1), and (B2). 2. The c-Met binding nucleic acid molecule according to claim 1 , wherein the polynucleotide (B2) is a polynucleotide comprising a base sequence obtained by deletion of three bases from the 3′ end in the base sequence of any one of SEQ ID NOs: 39 to 76.3. The c-Met binding nucleic acid molecule according to claim 1 , wherein the polynucleotide (B2) is a polynucleotide comprising a base sequence of any one of SEQ ID NOs: 81 to 89.4. The c-Met binding nucleic acid molecule according to claim 1 , wherein the polynucleotide (B2) is a polynucleotide comprising a base sequence obtained by deletion of three bases from the 3′ end in the base sequence of any one of SEQ ID NOs: 81 to 89.5. The c-Met binding nucleic acid molecule according to claim 1 , wherein the nucleic acid molecule comprises a modified nucleotide residue.6. The c-Met binding nucleic acid molecule according to claim 5 , wherein the modified nucleotide residue is at least one selected from the group consisting of methylated nucleotide residues claim 5 , fluorinated nucleotide residue claim 5 , aminated nucleotide residues claim 5 , and thiated nucleotide residues.7. The c-Met binding nucleic acid molecule according to claim 5 , wherein the modified nucleotide residue is at least one of a nucleotide residue with cytosine and a nucleotide residue with uracil.8. The c-Met binding nucleic acid molecule according to claim 5 , wherein the modified nucleotide residue is a nucleotide residue with a modified ribose residue.9. The c-Met binding nucleic acid molecule according to claim 1 , wherein the total ...

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16-05-2013 дата публикации

METHODS OF PREPARING TARGETED APTAMER PRODRUGS

Номер: US20130123478A1
Принадлежит:

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. 1. A process of preparing a nucleoside-containing- and/or nucleoside analog-containing-oligonucleotide for selective introduction into a subject's cells , the method comprising selecting a targeted aptamer , internalizing nucleic acid or tumor-homing nucleic acid via iterative rounds of selection against the cells or against the cells corresponding to the subject's cells to which the oligonucleotide is to be selectively introduced , and (i) hybridizing the nucleoside-containing- and/or nucleoside analog-containing-oligonucleotide to the targeted aptamer , internalizing nucleic acid or tumor-homing nucleic acid; (ii) replacing one or more nucleotide(s) with a nucleoside(s) and/or nucleoside analog(s) so as to prepare the nucleoside-containing- and/or nucleoside analog-containing-oligonucleotide; or (iii) synthesizing the targeted aptamer , internalizing nucleic acid or tumor-homing nucleic acid with one or more nucleoside or nucleoside analog(s) so as to prepare the nucleoside-containing- and/or nucleoside ...

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16-05-2013 дата публикации

Soluble TNF Receptors and Their Use in Treatment of Disease

Номер: US20130123479A1
Принадлежит:

The present invention relates to tumor necrosis factor (TNF) antagonists and corresponding nucleic acids derived from tumor necrosis factor receptors (TNFRs) and their use in the treatment of inflammatory diseases. These proteins are soluble secreted decoy receptors that bind to TNF and prevent TNF from signaling to cells. In particular, the proteins are mammalian TNFRs that lack exon 7 and which can bind TNF and can act as a TNF antagonist. 156.-. (canceled)57. An oligomer having a nucleoside sequence selected from the group consisting of: CCACAATCAGTCCTAG (SEQ ID NO: 14) , CACAATCAGTCCTA (SEQ ID NO: 21) and ACAATCAGTCCT (SEQ ID NO: 23) , having alternating 2′-deoxy- and 2′-O-4′-(methylene)-bicyclic-ribonucleosides , wherein the 5′-terminal nucleoside is a 2′-O-4′-(methylene)-bicyclic-ribonucleoside and the 3′-terminal nucleoside is a 2′-deoxyribonucleoside and wherein the internucleoside linkages are phosphorothioate linkages. This application is a continuation-in-part of U.S. application Ser. No. 11/595,485, filed Nov. 10, 2006 which claims priority to U.S. Provisional application Ser. No. 60/862,350, filed Oct. 20, 2006, and U.S. Provisional application Ser. No. 60/735,429, filed Nov. 10, 2005, all of which are incorporated by reference herein in their entirety.The present invention relates to tumor necrosis factor (TNF) antagonists and corresponding nucleic acids derived from TNF receptors and their use in the treatment of inflammatory diseases. These proteins are soluble secreted decoy receptors that bind to TNF-α and prevent TNF-α from signaling to cells.TNF-α is a pro-inflammatory cytokine that exists as a membrane-bound homotrimer and is released as a homotrimer into the circulation by the protease TNF-α converting enzyme (TACE). TNF-α is introduced into the circulation as a mediator of the inflammatory response to injury and infection. TNF-α activity is implicated in the progression of inflammatory diseases such as rheumatoid arthritis, Crohn's disease, ...

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16-05-2013 дата публикации

Multicomponent Nucleic Acid Enzymes And Methods For Their Use

Номер: US20130123480A1
Принадлежит: SPEEDX PTY LTD

The present invention relates to Multicomponent Nucleic Acid Enzymes (MNAzymes) and methods for their use. MNAzymes comprise two or more oligonucleotide components which self-assemble in the presence of one or more MNAzyme assembly facilitator molecules to form a catalytically active structure. Compositions for making MNAzymes, and collections of MNAzymes are provided. Also provided are methods for using MNAzymes for the detection, identification and/or quantification of one or more targets. The methods can be practiced in solution-based assays or in assays where one or more reaction components are attached to a support structure. The methods allow for multiplexing the MNAzyme detection to detect multiple targets in a single reaction. Also provided are kits for making the compositions, and for practicing the methods provided herein. 1. A method of producing a multi-component nucleic acid enzyme (MNAzyme) and determining whether the MNAzyme has catalytic activity , the method comprising:selecting a point at which to split a nucleic acid enzyme catalytic core nucleotide sequence for generation of first and second partial catalytic core portions on opposing sides of the point; 'wherein the first component oligonucleotide and the second component oligonucleotide self-assemble to form the MNAzyme upon hybridization of the MNAzyme assembly facilitator to the sensor arm portions of the first and second component oligonucleotides, thereby maintaining the first and second oligonucleotide components in proximity for association of their respective partial catalytic core portions to form the catalytic core of the MNAzyme, and allowing the substrate arm portions of the first and second component oligonucleotides to each hybridize with the substrate facilitating potential modification of the substrate by the catalytic core; and', 'contacting a first component oligonucleotide comprising the first partial catalytic core portion between a substrate arm portion and a sensor arm ...

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16-05-2013 дата публикации

MODIFIED NUCLEOSIDES, NUCLEOTIDES, AND NUCLEIC ACIDS, AND USES THEREOF

Номер: US20130123481A1
Принадлежит: Moderna Therapeutics

The present disclosure provides modified nucleosides, nucleotides, and nucleic acids, and methods of using them. 1. An isolated mRNA encoding a polypeptide of interest , said isolated mRNA comprising at least a first and a second modified nucleoside; wherein said first modified nucleoside is N1-methylpseudouridine and said second modified nucleoside is neither pseudouridine or 5-methylcytosine.2. The isolated mRNA of claim 1 , wherein a second modified nucleoside is selected from the group consisting of a modified purine nucleoside and a modified pyrimidine nucleoside.3. The isolated mRNA of claim 2 , wherein the second modified nucleoside is a modified purine nucleoside and the modified purine nucleoside is selected from the group consisting of adenosine and guanosine.4. The isolated mRNA of claim 3 , wherein the modified purine nucleoside comprises at least one modification selected from the group consisting of a base modification and a sugar modification.5. The isolated mRNA of claim 4 , wherein the at least one modification is on the sugar.6. The isolated mRNA of claim 2 , wherein the modified pyrimidine nucleoside is selected from the group consisting of cytidine and uridine.7. The isolated mRNA of claim 6 , wherein the modified pyrimidine nucleoside comprises at least one modification selected from the group consisting of a base modification and a sugar modification.8. The isolated mRNA of claim 7 , wherein the at least one modification is on the sugar.9. The isolated mRNA of further comprising a third modified nucleoside.10. The isolated mRNA of claim 9 , wherein the third modified nucleoside is selected from the group consisting of a modified purine nucleoside and a modified pyrimidine nucleoside.11. The isolated mRNA of claim 10 , wherein the third modified nucleoside is purine and the modified purine nucleoside comprises at least one modification selected from the group consisting of a base modification and a sugar modification.12. The isolated mRNA of ...

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16-05-2013 дата публикации

NUCLEOTIDE AND/OR OLIGONUCLEOTIDE AND PREPARATION PROCESS THEREOF

Номер: US20130123482A1
Принадлежит: SUZHOU RIBO LIFE SCIENCE CO., LTD

Nucleotide and/or oligonucleotide represented by formula (1) and the liquid phase synthesis process thereof. The present invention provides a liquid phase synthesis process for preparing a nucleotide and/or an oligonucleotide, comprising a process for combining the nucleotide and/or oligonucleotide protective groups, in which, under the condition that the 2′-hydroxyl group is protected by a group with a sterically hindered silane structure, the 3′ phosphate group(s) of the nucleotide and/or oligonucleotide is/are directly protected by (a)β-cyanoethyl group(s), and after the β-cyanoethyl group(s) is/are removed, the resulting product can directly participate in the next cycle of synthesis, wherein the synthesis reaction is carried out in a reaction flask or reaction kettle, without being limited by a solid carrier or synthesizer, so that the large scale preparation of oligonucleotides can be achieved. 2. The nucleotide and/or oligonucleotide according to claim 1 , wherein Ris tert-butyl dimethyl silicomethane group claim 1 , phenyl dimethyl silicomethane group claim 1 , tert-butyl diphenyl silicomethane group or triisopropyl silicomethane group.3. The nucleotide and/or oligonucleotide according to claim 1 , wherein the acyl is benzoyl claim 1 , isobutyryl or acetyl; the halogen atom is Cl or Br.5. The process according to claim 4 , wherein the acyl is benzoyl claim 4 , isobutyryl or acetyl; the alkyl groups in the trialkylammonium ion or dialkylammonium ion are identical or different and each has 1-6 carbon atoms.6. The process according to claim 4 , wherein the condensing agent is one or more of 1-mesitylene-sulfonyl-triazole claim 4 , 1-mesitylene-sulfonyl-(3-nitro)-triazole claim 4 , 1-mesitylene-sulfonyl-tetrazole claim 4 , 1-triisopropyl-phenyl-sulphonyl-triazole claim 4 , 1-triisopropyl-phenyl-sulphonyl-(3-nitro)-triazole and 1-triisopropyl-phenyl-sulphonyl-tetrazole; and the first liquid reaction medium is one or more of pyridine claim 4 , dichloromethane ...

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16-05-2013 дата публикации

Photogenerated reagents

Номер: US20130123486A1
Автор: GAO Xiaolian
Принадлежит:

This invention describes reagent precursors and methods for chemical and biochemical reactions. These reagent precursors that can be activated in solution upon irradiation to generate reagents required for the subsequent chemical reactions. Specifically, photogenerated reagents (PGR) are useful for controlling parallel combinatorial synthesis and various chemical and biochemical reactions. 164-. (canceled)65. A method for forming a nucleic acid polymer comprising:(a) derivatizing a solid surface with a protected moiety containing at least one protective group;(b) contacting the solid surface with solution comprising at least one photogenerated reagent precursor and at least one co-reagent;(c) irradiating the solution thereby generating a photogenerated reagent in at least a portion of the solution such that the protective group is removed from the protected moiety; and(d) coupling a nucleic acid monomer to the deprotected moiety.661. The method of claim wherein the photogenerated reagent precursor is a photogenerated reagent acid precursor.671. The method of claim wherein the co-reagent is a base.681. The method of claim wherein the protected moiety is a protected nucleotide.691. The method of claim wherein the photogenerated reagent precursor is a photogenerated reagent base precursor.701. The method of claim wherein the co-reagent is an acid.711. The method of claim wherein the protected moiety is a protected nucleic acid.721. The method of claim wherein the co-reagent is a sensitizer or supersensitizer.73. A method of deprotecting protected nucleic acids attached to a solid surface and wherein the nucleic acids have one or more protecting group(s) comprising a) contacting the protecting group moieties with a solution comprising one or more PGR-P(s) and one or more co-reagent(s) and b) irradiating the solution to produce one or more PGR(s) wherein the PGR(s) remove the protecting group(s) from the protected nucleic acids.749. The method of claim wherein the ...

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23-05-2013 дата публикации

Bioinformatically detectable group of novel viral regulatory genes and uses thereof

Номер: US20130130231A1
Автор: Bentwich Isaac
Принадлежит:

The present invention relates to a group of novel viral RNA regulatory genes, here identified as “viral genomic address messenger genes” or “VGAM genes”, and as “genomic address genes” or “GR” genes. VGAM genes selectively inhibit translation of known host target genes, and are believed to represent a novel pervasive viral attack mechanism. GR genes encode an operon-like cluster of VGAM genes. VGAM and viral GR genes may therefore be useful in diagnosing, preventing and treating viral disease. Several nucleic acid molecules are provided respectively encoding several VGAM genes, as are vectors and probes both comprising the nucleic acid molecules, and methods and systems for detecting VGAM genes, and for counteracting their activity. 1. A bioinformatically detectable novel viral gene encoding substantially pure nucleic acid wherein:a) RNA encoded by said bioinformatically detectable novel viral gene is about 18 to about 24 nucleotides in length, and originates from an RNA precursor, which RNA precursor is about 50 to about 120 nucleotides in length;b) a nucleotide sequence of a first half of said RNA precursor is a partial inversed-reversed sequence of a nucleotide sequence of a second half thereof;c) a nucleotide sequence of said RNA encoded by said novel viral gene is a partial inversed-reversed sequence of a nucleotide sequence of a binding site associated with at least one host target gene; andd) a function of said novel viral gene is bioinformatically deducible.2. A bioinformatically detectable novel viral gene encoding substantially pure DNA wherein:a) RNA encoded by said bioninformatically detectable novel viral gene comprises a plurality of RNA sections, each of said RNA sections being about 50 to about 120 nucleotides in length, and comprising an RNA segment, which RNA segment is about 18 to about 24 nucleotides in length;b) a nucleotide sequence of a first half of each of said RNA sections encoded by said novel gene is a partial inversed-reversed sequence ...

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23-05-2013 дата публикации

MicroRNA and Methods for Inhibiting Same

Номер: US20130130370A1
Принадлежит: THE ROCKEFELLER UNIVERSITY

The invention relates to isolated DNA or RNA molecules comprising at least ten contiguous bases having a sequence in a pancreatic islet microRNA. In another embodiment, the invention relates to isolated single stranded pancreatic islet microRNA molecules or anti-pancreatic islet microRNA molecules. 1. An isolated nucleic acid molecule comprising a maximum of fifty moieties , wherein each moiety comprises a base bonded to a backbone unit , said molecule comprising the sequence of bases identified in SEQ. ID. NO. 9.2. A molecule according to claim 1 , wherein at least one of the moieties is a modified deoxyribonucleotide moiety.3. A molecule according to wherein the modified deoxyribonucleotide is a phosphorothioate deoxyribonucleotide moiety.4. A molecule according to claim 2 , wherein the modified deoxyribonucleotide is a N′3-N′5 phosphoroamidate deoxyribonucleotide moiety.5. A molecule according to claim 1 , wherein at least one of the moieties is a modified ribonucleotide moiety.6. A molecule according to claim 5 , wherein the modified ribonucleotide is substituted at the 2′ position.7. A molecule according to claim 6 , wherein the substituent at the 2′ position is a Cto Calkyl group.8. A molecule according to claim 7 , wherein the alkyl group is methyl.9. A molecule according to claim 7 , wherein the alkyl group is allyl.10. A molecule according to claim 6 , wherein the substituent at the 2′ position is a Cto Calkoxy-Cto Calkyl group.11. A molecule according to claim 10 , wherein the Cto Calkoxy-Cto Calkyl group is methoxyethyl.12. A molecule according to claim 5 , wherein the modified ribonucleotide has a methylene bridge between the 2′-oxygen atom and the 4′-carbon atom.13. A molecule according to claim 1 , wherein at least one of the moieties is a peptide nucleic acid moiety.14. A molecule according to claim 1 , wherein at least one of the moieties is a 2′-fluororibonucleotide moiety.15. A molecule according to claim 1 , wherein at least one of the moieties is ...

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23-05-2013 дата публикации

NOVEL SIRNA STRUCTURE FOR MINIMIZING OFF-TARGET EFFECTS CAUSED BY ANTISENSE STRANDS, AND USE THEREOF

Номер: US20130130377A1
Автор: Lee Dong Ki, Pooja Dua

The present invention relates to a novel siRNA structure and the use thereof, and more particularly to a double-stranded siRNA molecule comprising an antisense strand and a sense strand, wherein the siRNA molecule has at least one single nucleotide bulge formed by introducing a single nucleotide into the antisense strand, particularly at position 2 from the 5′ end, and to a method of using the same to silence a target gene. The siRNA molecule of the invention shows high target gene silencing efficiency while minimizing off-target effects caused by the antisense strand, and thus has improved target selectivity. Accordingly, the siRNA molecule of the invention can be substituted for conventional siRNA molecules and can be widely be used in siRNA-based gene silencing techniques, including gene therapy. 1. A double-stranded siRNA molecule comprising an antisense strand and a sense strand complementary to the antisense strand , wherein the siRNA molecule has at least one single nucleotide bulge formed by introducing a single nucleotide into the antisense strand.2. The double-stranded siRNA molecule of claim 1 , wherein the single nucleotide bulge is present in the 5′ end region or 3′ end region of the antisense strand of the siRNA.3. The double-stranded siRNA molecule of claim 2 , wherein the 5′ end region of the antisense strand of the siRNA comprises nucleotides at positions 2 to 4 from the 5′ end.4. The double-stranded siRNA molecule of claim 2 , wherein the 3′ end region of the antisense strand of the siRNA comprise nucleotides at positions 2 to 4 from the 3′ end.5. The double-stranded siRNA molecule of claim 1 , wherein single nucleotide bulge is present at a position 2 from the 5′ end region of the antisense strand of the siRNA.6. The double-stranded siRNA molecule of claim 1 , wherein the introduced nucleotide is a nucleotide having a base different from that of a nucleotide which is adjacent thereto or an abasic nucleotide.7. The double-stranded siRNA molecule of ...

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23-05-2013 дата публикации

OLIGONUCLEOTIDES COMPRISING ACYCLIC AND ABASIC NUCLEOSIDES AND ANALOGS

Номер: US20130130378A1
Принадлежит: ALNYLAM PHARMACEUTICALS, INC.

This invention relates to acyclic and abasic nucleosides and oligonucleotides prepared therefrom. For instance, oligonucleotides can be prepared having one or more of the following formulas (I-III):, or isomers thereof. 54. The monomer of any of - claims 1 , wherein Ris a protecting group and Ris a reactive phosphorous group or solid support.64. The monomer of any of - claims 1 , wherein Ris a reactive phosphorous group or solid support and Ris a protecting group.76. The monomer of any of - claims 1 , wherein the reactive phosphorus group is selected from the group consisting of phosphoramidite claims 1 , H-phosphonate claims 1 , alkyl-phosphonate claims 1 , and phosphate triester.87. The monomer of any of - claims 1 , wherein the protecting group is a hydroxyl protecting group selected from the group consisting of acetyl claims 1 , benzyl claims 1 , t-butyldimethylsilyl claims 1 , t-butyldiphenylsilyl claims 1 , trityl claims 1 , monomethoxytrityl claims 1 , and dimethoxytrityl.98. An oligonucleotide comprising at least one monomer of any of -.16. The oligonucleotide of claim 15 , wherein n1 or n2 is 1-20.1716. The oligonucleotide of any of - claims 9 , wherein the monomer is at the 5′-end terminal position of the oligonucleotide.1816. The oligonucleotide of any of - claims 9 , wherein the monomer is at the 3′-end terminal position of the oligonucleotide.1916. The oligonucleotide of any of - claims 9 , wherein the monomer is at an internal position of the oligonucleotide.2016. The oligonucleotide of any of - claims 9 , wherein the monomer is at both the 5′- and 3′-end terminal position of the oligonucleotide.2116. The oligonucleotide of any of - claims 9 , wherein the monomer is present at the 5′-end terminal position and at least one internal position of the oligonucleotide.2216. The oligonucleotide of any of - claims 9 , wherein the monomer is present at the 3′-end terminal position and at least one internal position of the oligonucleotide.2316. The ...

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23-05-2013 дата публикации

RTP801L SIRNA COMPOUNDS AND METHODS OF USE THEREOF

Номер: US20130131143A1
Принадлежит: QUARK PHARMACEUTICALS, INC.

The invention provides chemically modified siRNA oligonucleotides that target RTP801L, compositions comprising same and to the use of such molecules to treat, inter alia, respiratory diseases including acute and chronic pulmonary disorders, eye diseases including glaucoma and ION, microvascular disorders, angiogenesis- and apoptosis-related conditions, and hearing impairments. 2. (canceled)3. The double-stranded RNA compound of claim 1 , wherein (N)x comprises 2′-O-methyl sugar modified ribonucleotides at positions 1 claim 1 , 3 claim 1 , 5 claim 1 , 7 claim 1 , 9 claim 1 , 11 claim 1 , 13 claim 1 , 15 claim 1 , 17 and 19.4. The double-stranded RNA compound of claim 1 , wherein (N)x comprises 2′-O-methyl sugar modified ribonucleotides at positions 2 claim 1 , 4 claim 1 , 6 claim 1 , 8 claim 1 , 11 claim 1 , 13 claim 1 , 15 claim 1 , 17 claim 1 , and 19.5. The double-stranded RNA compound of claim 2 , wherein (N′)y comprises a mirror nucleotide.6. The double-stranded RNA compound of claim 5 , wherein the mirror nucleotide is present at position 18.7. The double-stranded RNA compound of claim 6 , wherein (N′)y further comprises a mirror nucleotide at position 17.8. The double-stranded RNA compound of or claim 6 , wherein (N′)y comprises a deoxyribonucleotide at position 15.9. The double-stranded RNA compound of claim 1 , wherein each of (N)x and (N′)y is unphosphorylated or phosphorylated at the 5′ terminus and the 3′ terminus.10. The double-stranded RNA compound of claim 9 , wherein (N)x is unphosphorylated at the 3′ terminus.11. The double-stranded RNA of claim 1 , wherein z″ is present.1314.-. (canceled)15. A composition comprising the double-stranded RNA compound of or ; and a pharmaceutically acceptable carrier.1628.-. (canceled)29. The double-stranded RNA compound of claim 1 , wherein the covalent bond joining each consecutive N or N′ is a phosphodiester bond.30. The double-stranded RNA compound of claim 12 , wherein the sense strand comprises at least one ...

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23-05-2013 дата публикации

SUBSTITUTED 2'-AMINO AND 2'-THIO-BICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM

Номер: US20130131147A1
Принадлежит: Isis Pharmaceuticals, Inc.

Provided herein are 2′-amino and 2′-thio bicyclic nucleosides and oligomenc compounds prepared therefrom. The novel bicyclic nucleosides provided herein are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as nuclease resistance. 192-. (canceled)94. The bicyclic nucleoside of wherein Bx is an optionally protected uracil claim 93 , thymine claim 93 , cytosine claim 93 , 5-methylcytosine claim 93 , adenine or guanine.95. The bicyclic nucleoside of wherein Tis 4 claim 93 ,4′-dimethoxytrityl and Tis diisopropylcyanoethoxy phosphoramidite.96. The bicyclic nucleoside of wherein Qand Qare each H.97. The bicyclic nucleoside of wherein one of Qand Qis H and the other of Qand Qis C-Calkyl or substituted C-Calkyl.98. The bicyclic nucleoside of wherein one of Qand Qis CH.99. The bicyclic nucleoside of wherein Gand Gare each H.100. The bicyclic nucleoside of wherein one of Gand Gis H and the other of Gand Gis C-Calkyl or substituted C-Calky.101. The bicyclic nucleoside of wherein at least one of Gand Gis CH.102. The bicycle nucleoside of wherein Z is NR wherein R is H claim 93 , C-Csubstituted C-Calkyl claim 93 , C-Calkoxy or substituted C-Calkoxy.103. The bicyclic nucleoside of wherein R is CHor methoxy.104. The bicyclic nucleoside of wherein Z is S.106. The bicyclic nucleoside of wherein three of Q claim 105 , Q claim 105 , Gand Gare H and the other one of Q claim 105 , Q claim 105 , Gand Gis CH.107. The bicyclic nucleoside of wherein two of Q claim 105 , Q claim 105 , Gand Gare H and the remaining two of Q claim 105 , Q claim 105 , Gand Gare CHwherein the two that are CHare selected from Qand G claim 105 , Qand G claim 105 , Qand G claim 105 , and Qand G.109. The oligomeric compound of wherein Bx is an optionally protected uracil claim 108 , thymine claim 108 , cytosine claim 108 , 5-methylcytosine claim 108 , adenine or guanine for each bicyclic nucleoside of Formula II.110. The oligomeric compound of ...

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23-05-2013 дата публикации

METHODS AND COMPOSITIONS FOR DETECTING GASTROINTESTINAL AND OTHER CANCERS

Номер: US20130131329A1
Принадлежит: CASE WESTERN RESERVE UNIVERSITY

This application describes methods and compositions for detecting and treating vimentin-associated neoplasia. Differential methylation of the vimentin nucleotide sequences has been observed in vimentin-associated neoplasia such as neoplasia of the upper or lower gastrointestinal tract, pancreas, and/or bladder. 136-. (canceled)37. An isolated polynucleotide fragment derived from a methylated vimentin gene , wherein said polynucleotide fragment is a fragment that is derived from a methylated nucleotide sequence that is at least 90% identical to the nucleotide sequence of SEQ ID NO: 51 , and wherein said fragment comprises at least a portion of a nucleotide sequence that is at least 90% identical to the methylated nucleotide sequence of SEQ ID NO: 41 , SEQ ID NO: 42 , SEQ ID NO: 44 , and/or SEQ ID NO: 45 or complements thereof.38. The isolated polynucleotide of claim 37 , wherein said polynucleotide consists of the nucleotide sequence of SEQ ID NO: 41 claim 37 , SEQ ID NO: 42 claim 37 , SEQ ID NO: 44 claim 37 , and/or SEQ ID NO: 45 claim 37 , or a fragment thereof and/or a complement thereof.39. The isolated polynucleotide of claim 38 , wherein said polynucleotide consists of the nucleotide sequence of SEQ ID NO: 41 claim 38 , or a fragment thereof and/or a complement thereof.40. The isolated polynucleotide of claim 38 , wherein said polynucleotide consists of the nucleotide sequence of SEQ ID NO: 42 claim 38 , or a fragment thereof and/or a complement thereof.41. The isolated polynucleotide of claim 38 , wherein said polynucleotide consists of the nucleotide sequence of SEQ ID NO: 44 claim 38 , or a fragment thereof and/or a complement thereof.42. The isolated polynucleotide of claim 38 , wherein said polynucleotide consists of the nucleotide sequence of SEQ ID NO: 45 claim 38 , or a fragment thereof and/or a complement thereof.43. The isolated polynucleotide of claim 42 , wherein said complement thereof consists of the nucleotide sequence of SEQ ID NO: 48 claim 42 , ...

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30-05-2013 дата публикации

OLIGODEOXYNUCLEOTIDE AND ITS USE TO INDUCE AN IMMUNE RESPONSE

Номер: US20130136771A1

A substantially pure or isolated oligodeoxynucleotide of at least 10 nucleotides is disclosed, wherein the oligodeoxynucleotide comprised a sequence represented by either formula: 1. A substantially pure or isolated oligodeoxynucleotide , wherein the oligodeoxynucleotide comprises the nucleic acid sequence set forth as SEQ ID NO: 22 , and wherein the oligodeoxynucleotide is 100 nucleotides or less in length.2. The oligodeoxynucleotide of claim 1 , wherein the oligodeoxynucleotide is modified to prevent degradation.3. The oligodeoxynucleotide of claim 1 , wherein the oligodeoxynucleotide has a phosphate backbone modification.4. The oligodeoxynucleotide of claim 3 , wherein the phosphate backbone modification is a phosphorothioate backbone modification.5. The oligodeoxynucleotide of claim 1 , wherein the oligodeoxynucleotide is 20 nucleotides in length.6. The oligodeoxynucleotide claim 1 , wherein the oligodeoxynucleotide is 50 nucleotides or less in length.7. The oligodeoxynucleotide of claim 1 , wherein the oligodeoxynucleotide is 30 nucleotides or less in length.8. An oligodeoxynucleotide delivery complex comprising the oligodeoxynucleotide of and a targeting means.9. The oligodeoxynucleotide delivery complex of claim 8 , wherein the targeting means is selected from the group consisting of cholesterol claim 8 , virosome claim 8 , liposome claim 8 , lipid claim 8 , and a target cell specific binding agent.10. A composition comprising the oligodeoxynucleotide of and a pharmacologically acceptable carrier.11. A method of inducing cytokine production by a peripheral blood mononuclear cell claim 1 , comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting the peripheral blood mononuclear cell with an effective amount of the oligodexoynucleotide of , thereby inducing the production of the cytokine, wherein the cytokine is interleukin (IL)-6 or interferon γ.'}12. The method of claim 11 , wherein the oligodeoxynucleotide is 30 nucleotides or less in length. ...

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30-05-2013 дата публикации

DNA-LINKED NANOPARTICLE BUILDING BLOCKS FOR NANOSTRUCTURE ASSEMBLY AND METHODS OF PRODUCING THE SAME

Номер: US20130136925A1
Принадлежит:

A method of producing a nanoparticle assembly. The method includes attaching a first DNA molecule to a bead to form a first DNA-bead complex; and combining a nanoparticle with the first DNA-bead complex to form a nanoparticle-DNA-bead complex having one DNA molecule attached to the nanoparticle. 1. A method of producing a nanoparticle assembly , comprising:attaching a first DNA molecule to a bead to form a first DNA-bead complex; andcombining a nanoparticle with the first DNA-bead complex to form a first nanoparticle-DNA-bead complex having one DNA molecule attached to the nanoparticle.2. The method of claim 1 , further comprising releasing the bead from the first nanoparticle-DNA-bead complex to form a first nanoparticle-DNA complex having one DNA molecule attached to the nanoparticle.3. The method of claim 2 , further comprising:attaching a second DNA molecule to a bead to form a second DNA-bead complex; andcombining the first nanoparticle-DNA complex with the second DNA-bead complex to form a second nanoparticle-DNA-bead complex having two DNA molecules attached to the nanoparticle.4. The method of claim 3 , further comprising releasing the bead from the second nanoparticle-DNA-bead complex to form a second nanoparticle-DNA complex having two DNA molecules attached to the nanoparticle claim 3 , wherein the DNA molecules in the second nanoparticle-DNA complex are approximately parallel to one another.5. The method of claim 4 , further comprising:attaching a third DNA molecule to a bead to form a third DNA-bead complex; andcombining the second nanoparticle-DNA complex with the third DNA-bead complex to form a third nanoparticle-DNA-bead complex having three DNA molecules attached to the nanoparticle.6. The method of claim 5 , further comprising releasing the bead from the third nanoparticle-DNA-bead complex to form a third nanoparticle-DNA complex having three DNA molecules attached to the nanoparticle claim 5 , wherein two of the three DNA molecules in the third ...

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30-05-2013 дата публикации

Rapid nucleic acid purification

Номер: US20130137107A1
Принадлежит: Nanohelix Co Ltd

Provided is a method for rapid nucleic acid purification, and the method for rapid nucleic acid isolation according to the present invention is very useful in diagnosing causes of disease or detecting a target gene; can be used in molecular diagnosis of causes of disease more rapidly and conveniently, as compared with the existing nucleic acid isolation method requiring complicated and special equipment; does not require skills therefor, thereby allowing an ordinary person to personally conduct isolation of nucleic acid for analyzing causes of disease and further solving the existing inconvenience caused by directly going to the hospitals or health clinical centers; and can analyze causes of disease more promptly.

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06-06-2013 дата публикации

IMMUNOSTIMULATORY SEQUENCE OLIGONUCLEOTIDES AND METHODS OF USING THE SAME

Номер: US20130142814A1
Принадлежит:

The invention provides immunomodulatory polynucleotides and methods for immunomodulation of individuals using the immunomodulatory polynucleotides. 2. An immunomodulatory polynucleotide according to wherein the palindromic sequence has a base composition of more than one-third A's and T's.3. An immunomodulatory polynucleotide according to wherein the wherein the IMP comprises a sequence selected from the group consisting of SEQ ID NO: 172 claim 1 , SEQ ID NO: 55 claim 1 , SEQ ID NO: 113 claim 1 , SEQ ID NO: 38 claim 1 , SEQ ID NO: 39 claim 1 , SEQ ID NO: 53 claim 1 , SEQ ID NO: 109 claim 1 , SEQ ID NO: 117 claim 1 , SEQ ID NO: 175 claim 1 , SEQ ID NO: 45 claim 1 , SEQ ID NO: 75 claim 1 , and SEQ ID NO: 44.4. An immunomodulatory composition comprising an immunomodulatory polynucleotide according to or .5. A method of modulating an immune response in an individual comprising: administering to an individual an immunomodulatory polynucleotide according to or in an amount sufficient to modulate an immune response in said individual.6. A method of increasing interferon-gamma (IFN-γ) in an individual claim 1 , comprising: administering an immunomodulatory polynucleotide according to according to or to said individual in an amount sufficient to increase IFN-γ in said individual.7. A method of increasing interferon-alpha (IFN-α) in an individual claim 1 , comprising: administering an immunomodulatory polynucleotide according to or to said individual in an amount sufficient to increase IFN-α in said individual.8. A method of ameliorating a symptom of an infectious disease in an individual claim 1 , comprising:{'claim-ref': [{'@idref': 'CLM-00001', 'claim 1'}, {'@idref': 'CLM-00003', '3'}], 'administering an effective amount of an immunomodulatory polynucleotide according to or to the individual, wherein an effective amount is an amount sufficient to ameliorate a symptom of said infectious disease.'}9. A method of ameliorating a symptom of an IgE-related disorder in an ...

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06-06-2013 дата публикации

Methods and compositions for high yield, specific amplification

Номер: US20130143219A1
Принадлежит: MEDICAL COLLEGE OF WISCONSIN

The present invention is directed to methods and compositions for amplifying nucleic acids. Included in the present invention are methods and compositions that amplify nucleic acids with high yield with the formation of unstable target extension products, preferably with minimal or no introduction of allelic bias. Also included in the present invention are high yield, instability primers for use in amplification methods, as multiplexed amplification methods.

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06-06-2013 дата публикации

MODULATION OF GLUCOCORTICOID RECEPTOR EXPRESSION

Номер: US20130143943A1
Принадлежит: Isis Pharmaceuticals, Inc.

Compounds, compositions and methods are provided for modulating the expression of glucocorticoid receptor. The compositions comprise oligonucleotides, targeted to nucleic acid encoding glucocorticoid receptor. Methods of using these compounds for modulation of glucocorticoid receptor expression and for diagnosis and treatment of diseases and conditions associated with expression of glucocorticoid receptor are provided. 1. An antisense compound 12 to 50 nucleobases in length comprising at least one of a modified internucleoside linkage , a high affinity modified sugar or a modified nucleobase , wherein said antisense compound comprises a nucleobase sequence comprising at least 8 contiguous nucleobases complementary to an equal length portion of nucleobases 672-691 , nucleobases 679-698 , or nucleobases 687-706 of the nucleic acid molecule encoding human glucocorticoid receptor in SEQ ID NO: 4 , or an exon:intron region , an intron:exon region , or an intron of the nucleic acid molecule encoding human glucagon receptor in SEQ ID NO: 25 , wherein the nucleobase sequence of the antisense compound is at least 90% complementary to SEQ ID NOs: 4 or 25 over the entire length of the antisense compound.2. The compound of which is 15 to 30 nucleobases in length.3. The compound of which is 20 nucleobases in length.4. The compound of having at least 95% complementarity with SEQ ID NOs: 4 or 18 as measured over the entire length of the antisense compound.5. The compound of having at least one 2′-O-methoxyethyl sugar moiety.6. The compound of having at least one phosphorothioate internucleoside linkage.7. The compound of having at least one 5-methylcytosine.8. The compound of that is a pharmaceutically acceptable salt.9. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable diluent or carrier.10. The compound of claim 1 , comprising at least one high affinity modified sugar moiety selected from the group consisting of a 2′-O-(2-methoxyethyl) ...

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06-06-2013 дата публикации

Forensic identification

Номер: US20130144047A1
Принадлежит: QIAGEN GmbH

The invention provides allelic ladder mixtures and individual alleles suitable for use in such mixtures. The allelic ladder mixtures give improved identification and distinguishing capabilities, particularly suitable in forensic investigations.

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06-06-2013 дата публикации

Therapeutic compositions

Номер: US20130144048A1
Принадлежит: Alnylam Pharmaceuticals Inc

This application relates to therapeutic siRNA agents and methods of making and using the agents.

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13-06-2013 дата публикации

Methods, Reagents and Kits for Preservation of Nucleic Acids in Biological Samples

Номер: US20130149691A1
Автор: Haj-Ahmad Yousef
Принадлежит: Norgen Biotek Corp.

Provided is a nucleic acid preservative comprising at least one reducing agent, at least one chaotropic substance, at least one polyamine substance and at least one chelating agent and uses thereof, and a method for the preservation of nucleic acids in a biological sample. Further provided are kits for use in the preservation of nucleic acids in a biological sample, and more particularly, a blood sample. 1. A nucleic acid preservative comprising at least one reducing agent , at least one chaotropic substance , at least one polyamine substance and at least one chelating agent.2. The nucleic acid preservative according to claim 1 , wherein the reducing agent is glutathione and wherein the glutathione is present in an amount from about 10 mM to about 200 mM.3. The nucleic acid preservative according to claim 1 , wherein the chaotropic substance is a lithium salt and wherein the lithium salt is present in an amount from about 1 M to about 4 M.4. The nucleic acid preservative according to claim 3 , wherein the lithium salt is LiCl.5. The nucleic acid preservative according to claim 1 , wherein the chaotropic substance is a guanidium salt claim 1 , and wherein the guanidium salt is present in an amount from about 0.1 M to about 0.9 M.6. The nucleic acid preservative according to claim 5 , wherein the guanidium salt is guanidine hydrochloride.7. The nucleic acid preservative according to claim 1 , wherein the chaotropic substance is urea and wherein the urea is present in an amount from about 2 M to about 12 M.8. The nucleic acid preservative according to claim 1 , wherein the polyamine substance is spermidine and wherein the spermidine is present in an amount from about 10 μM to about 300 μM.9. The nucleic acid preservative according to claim 1 , wherein the polyamine substance is biuret and wherein the biuret is present in an amount of about 10 mM to about 100 mM.10. The nucleic acid preservative according to claim 1 , wherein the chelating agent is EDTA and wherein the ...

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13-06-2013 дата публикации

Translation Kinetic Mapping, Modification and Harmonization

Номер: US20130149699A1
Принадлежит:

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. 1. A method of adjusting the translation kinetics of an mRNA , the method comprising:selecting a codon from a wobbie codon pair, wherein within the pair, a codon that has G·C or I:C pairing with a cognate anticodon in the third position has increased speed of translation relative to a codon that has G·U or I:U pairing with a cognate anticodon in the third position.2. The method of claim 1 , wherein the wobble codon pair has G·C and G·U pairing.3. The method of claim 1 , wherein a starting polynucleotide sequence is substituted in at least one codon with respect to a wobble codon pair.4. The method of claim 3 , wherein said starting polynucleotide sequence is substituted in at least one member of a wobble codon pair to provide for G·C pairing to increase or decrease translation rate.5. The method of claim 4 , wherein said starting polynucleotide sequence is substituted in at least 20% of the codons that are wobble codons.6. The method of claim 4 , wherein said starting polynucleotide sequence is substituted in at least 50% of the codons that are wobble codons.7. The method of claim 3 , wherein the speed of translation is altered at least 10%.8. A method of de novo synthesis of a polynucleotide encoding a polypeptide of interest claim 3 , the method comprising:selecting a codon for each amino acid of the polypeptide of interest, wherein at least one codon is selected from a wobble codon pair, wherein within the pair, a codon that has G·C or I:C ...

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13-06-2013 дата публикации

CHEMICAL SYNTHESIS USING UP-CONVERTING PHOSPHOR TECHNOLOGY AND HIGH SPEED FLOW CYTOMETRY

Номер: US20130150265A1
Принадлежит:

The invention offers the ability to rapidly synthesize multiple chemical compounds, particularly polymers of varying sequences, in parallel on the surfaces of carrier beads. Tinvention involves attaching up-converting phosphors (UCP's) to beads to create up-converting phosphor-loaded beads (UCP-loaded beads) with unique spectral characteristics. Using a dynamic sorting architecture each bead is cataloged based on its spectral characteristics, assigned a compound or polymer to be synthesized, and subjected to multiple rounds of sorting by a flow cytometer, wherein each round sorts the bead to an appropriate bin for a selected chemical reaction, such as the attachment of a monomeric subunit of the polymer sequence. 1. A carrier bead having a generally spherical shape and a layer of at least one up-converting phosphor particle on the bead's surface.2. A bead according to claim 1 , wherein the bead has a metallic layer between the bead surface and the up-converting phosphor particle layer.3. A bead according to claim 1 , wherein the bead is a ceramic bead.4. A bead according to claim 1 , having an external coating encapsulating the bead and up-converting phosphor particle layer.5. A bead according to claim 4 , wherein the external coating is a silica coating claim 4 , a glass coating claim 4 , or a ceramic coating.6. A bead according to claim 1 , wherein the up-converting phosphor particle layer comprises at least two up-converting phosphor particles having distinct emission wavelengths.7. A bead of claim 1 , wherein the diameter of the bead core is any diameter up to about 20 μm.8. A bead of claim 7 , wherein the up-converting phosphor particles have a diameter of at least 50 nm claim 7 , at least 75 nm claim 7 , at least 100 nm claim 7 , or at least 300 nm.9. A bead according to claim 8 , having an external coating encapsulating the bead and up-converting phosphor particle layer.10. A bead according to claim 9 , wherein the external coating is a silica coating claim 9 ...

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