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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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Применить Всего найдено 27448. Отображено 100.

05-01-2012 дата публикации

Animal model for parkinson's disease

Номер: US20120005765A1

Автор: Michael Panneton, Vijaya Kumar, William Burke

Принадлежит: St Louis University

Disclosed are methods and compositions for an animal model of Parkinson's disease. In particular, disclosed is the use of antisense compounds to inhibit the expression of ALDH1A1 in the substantia nigra of an animal brain for the purpose of creating an animal that will displays the symptoms of a human with Parkinson's Disease, including various biochemical, histological, and behavioral characteristics. Also disclosed are methods for using the animal model for Parkinson's disease to test potential therapeutic agents for Parkinson's disease.

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Номер записи: 1

19-01-2012 дата публикации

Nucleic acid aptamers

Номер: US20120014875A1

Автор: Anton P. Mccaffrey, James O. McNamara, Paloma H. Giangrande

Принадлежит: University of Iowa Research Foundation UIRF

The present invention relates to optimized aptamers and methods of using these aptamers.

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Номер записи: 2

19-01-2012 дата публикации

Novel inhibitors of retroviral reverse transcriptace

Номер: US20120015874A1

Автор: Daniel Michalowski, Donald H. Burke-Aguero

Принадлежит: University of Missouri System

Disclosed are nucleic acid molecules, and methods of their use, which have a specific structure including a double helical domain and a G-quadruplex domain physically connected by a linker domain which may be nucleosidic or non-nucleosidic. These aptamers demonstrate potent inhibition of phylogenetically diverse primate lentiviral reverse transcriptases, which effect is largely independent of aptamer sequence provided that the aptamer has the specified structure.

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Номер записи: 3

26-01-2012 дата публикации

Short Interfering Ribonucleic Acid (siRNA) for Oral Administration

Номер: US20120022139A1

Автор: Christian Rene Schnell, Eric Billy, Francois Jean-Charles Natt, Juerg Hunziker

Принадлежит: NOVARTIS AG

Short interfering ribonucleic acid (siRNA) for oral administration, said siRNA comprising two separate RNA strands that are complementary to each other over at least 15 nucleotides, wherein each strand is 49 nucleotides or less, and wherein at least one of which strands contains at least one chemical modification.

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Номер записи: 4

26-01-2012 дата публикации

Folate targeting of nucleotides

Номер: US20120022245A1

Автор: Christopher Paul Leamon, Iontcho Radoslavov Vlahov, Longwu Qi, Mini Thomas, Paul Joseph Kleindl, Philip Stewart Low

Принадлежит: Endocyte Inc, PURDUE RESEARCH FOUNDATION

The present invention relates to compounds, compositions, kits, and methods of use in targeting nucleotides, such as siRNA's, to cancer cells or to immune system cells involved in inflammation. More particularly, the invention is directed to receptor binding ligand-nucleotide delivery conjugates for use in specifically targeting the conjugates to cancer cells or to immune system cells, methods of treatment with these conjugates, methods of preparation of these conjugates, and methods of reducing the expression of a gene in vitro or in vivo with the conjugates described herein.

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Номер записи: 5

02-02-2012 дата публикации

Novel lipids and compositions for the delivery of therapeutics

Номер: US20120027796A1

Автор: David Butler, Jayaprakash K. Narayanannair, Kallanthottathil G. Rajeev, Laxmab Eltepu, Muthiah Manoharan, Muthusamy Jayaraman

Принадлежит: Alnylam Pharmaceuticals Inc

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structures: (Formula (I) or (XXXV)).

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Номер записи: 6

02-02-2012 дата публикации

Short Interfering Ribonucleic Acid (siRNA) for Oral Administration

Номер: US20120029052A1

Автор: Christian Rene Schnell, Eric Billy, Francois Jean-Charles Natt, Juerg Hunziker

Принадлежит: NOVARTIS AG

Short interfering ribonucleic acid (siRNA) for oral administration, said siRNA comprising two separate RNA strands that are complementary to each other over at least 15 nucleotides, wherein each strand is 49 nucleotides or less, and wherein at least one of which strands contains at least one chemical modification.

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Номер записи: 7

01-03-2012 дата публикации

Splice-region antisense composition and method

Номер: US20120053228A1

Автор: Patrick L. Iversen, Robert Hudziak

Принадлежит: AVI Biopharma Inc

Antisense compositions targeted against an mRNA sequence coding for a selected protein, at a region having its 5′ end from 1 to about 25 base pairs downstream of a normal splice acceptor junction in the preprocessed mRNA, are disclosed. The antisense compound is RNase-inactive, and is preferably a phosphorodiamidate-linked morpholino oligonucleotide. Such targeting is effective to inhibit natural mRNA splice processing, produce splice variant mRNAs, and inhibit normal expression of the protein.

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Номер записи: 8

01-03-2012 дата публикации

Cationic poly (amino acids) and uses thereof

Номер: US20120053295A1

Автор: Hyunjin Kim, Kanjiro Miyata, Kazunori Kataoka, Nobuhiro Nishiyama, Shourong Wu, Takehiko Ishii

Принадлежит: University of Tokyo NUC

The present invention provides an efficient delivery system for a nucleic acid, more specifically, a cationic poly(amino acid) that has a side chain having a plurality of different amine functional groups in a moiety including a cationic group and that has a hydrophobic group introduced into part of the side chain, and a polyion complex (PIC) of the poly(amino acid) and an oligo- or polynucleotide.

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Номер записи: 9

08-03-2012 дата публикации

Inhibition of map4k4 through rnai

Номер: US20120059046A1

Автор: Anastasia Khvorova, Joanne Kamens, Tod M Woolf, William Salomon

Принадлежит: RXi Pharmaceuticals Corp

RNAi constructs directed to MAP4K4 that demonstrate unexpectedly high gene silencing activities, and uses thereof are disclosed. The blunt-ended constructs have a double-stranded region of 19-49 nucleotides. The constructs have selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the strands may be modified (e.g., one or both ends of the sense strand is modified by 2′-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, the antisense strand may also be modified by a 2′-O-methyl group at the penultimate 5′-end nucleotide to greatly reduce off-target silencing.

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Номер записи: 10

29-03-2012 дата публикации

Control of Gene Expression Using a Complex of an Oligonucleotide and a Regulatory Peptide

Номер: US20120077270A1

Автор: Andrew C.G. Porter, Boris Tumi PuFong, John David Jenkinson, Laki Buluwela, Patrick Kanda, Satu Vainikka, Simak Ali, Stephen Hart

Принадлежит: Imperial College Innovations Ltd

A method for suppressing the expression of a selected gene in a cell, the method comprising introducing into the cell a molecule comprising (1) a nucleic acid binding portion which binds to a site or associated with the selected gene which site is present in a genome and (2) an expression repressor portion, wherein the nucleic acid binding portion comprises an oligonucleotide or oligonucleotide mimic or analogue, and wherein the repressor portion comprises a polypeptide or peptidomimetic. Molecules for use in the methods of the invention are provided. The repressor may be a portion of a histone deacetylase or DNA methylase or polypeptide capable of recruiting a histone deacetylase or DNA methylase.

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Номер записи: 11

19-04-2012 дата публикации

Novel lipids and compositions for the delivery of therapeutics

Номер: US20120095075A1

Автор: David Butler, Kallanthottathil G. Rajeev, Laxman Eltepu, Muthiah Manoharan, Muthusamy Jayaraman, Narayanannair K. Jayaprakash

Принадлежит: Alnylam Pharmaceuticals Inc

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure:

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Номер записи: 12

10-05-2012 дата публикации

Anti-MicroRNA Oligonucleotide Molecules

Номер: US20120115220A1

Автор: Gunter Meister, Markus Landthaler, Sebastien Pfeffer, Thomas Tuschl

Принадлежит: ROCKEFELLER UNIVERSITY

The invention relates to isolated anti-microRNA molecules. In another embodiment, the invention relates to an isolated microRNA molecule. In yet another embodiment, the invention provides a method for inhibiting microRNP activity in a cell.

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Номер записи: 13

10-05-2012 дата публикации

Compositions and their uses directed to hepcidin

Номер: US20120115930A1

Автор: Brett P. Monia, C. Frank Bennett, Robert Mckay, Trisha Lockhart, William A. Gaarde

Принадлежит: ISIS PHARMACEUTICALS INC

Disclosed herein are compounds, compositions and methods for modulating the expression of hepcidin in a cell, tissue or animal or preventing, ameliorating or treating anemia. Also provided are methods for prevention, amelioration or treatment of anemia, and for increasing red blood cell count in an animal. Also provided are methods for the prevention, amelioration and/or treatment of low serum iron levels, low red blood cell count and other clinical endpoints of anemia in an animal. These methods may be achieved by administration of compounds or compositions including antisense compounds targeted to a nucleic acid that expresses hepcidin polypeptide combined with an erythropoiesis stimulating agent.

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Номер записи: 14

17-05-2012 дата публикации

Nucleic acid ligands to ll37

Номер: US20120121533A1

Автор: George W. Jackson

Принадлежит: Biotex Inc

The present invention is directed to nucleic acid ligands to LL37, methods for producing said nucleic acid ligands, and methods for utilizing said nucleic acid ligands. In one exemplary embodiment, for example, this invention relates to nucleic acid ligands exhibiting high specific binding affinity to LL37 peptides, precursors and/or portions thereof. Further, the nucleic acid ligands may bind competitively with native ligands of LL37 and may also inhibit and/or interfere with LL37 function, such as by binding to LL37.

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Номер записи: 15

17-05-2012 дата публикации

Rna sequence-specific mediators of rna interference

Номер: US20120122111A1

Автор: David P. Bartel, Phillip A. Sharp, Phillip D. Zamore, Thomas Tuschl

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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Номер записи: 16

24-05-2012 дата публикации

Skin Permeating And Cell Entering (SPACE) Peptides and Methods of Use Thereof

Номер: US20120128756A1

Автор: Samir M. Mitragotri, Tracy Hsu

Принадлежит: UNIVERSITY OF CALIFORNIA

The present disclosure provides peptides and peptide compositions, which facilitate the delivery of an active agent or an active agent carrier wherein the compositions are capable of penetrating the stratum corneum (SC) and/or the cellular membranes of viable cells.

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Номер записи: 17

24-05-2012 дата публикации

dsRNA For Treating Viral Infection

Номер: US20120129913A1

Автор: Jason Borawski, Larry Alexander Gaither, Mark Aron Labow

Принадлежит: NOVARTIS AG

The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression of phosphatidylinositol 4-kinase (PI4K), in particular human phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB) or human phosphatidylinositol 4-kinase, catalytic, alpha polypeptide (PIK4CA), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PIK4CB or PIK4CA target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes. The invention further includes methods for treating diseases caused by positive stranded RNA virus infection using the pharmaceutical compositions; and methods for inhibiting the propogation of positive stranded RNA viruses in and between cells.

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Номер записи: 18

31-05-2012 дата публикации

Treatment of 'c terminus of hsp70-interacting protein' (chip) related diseases by inhibition of natural antisense transcript to chip

Номер: US20120135941A1

Автор: Carlos Coito, Joseph Collard, Olga Khorkova Sherman

Принадлежит: Curna Inc

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of ‘C terminus of HSP70-Interacting Protein’ (CHIP), in particular, by targeting natural antisense polynucleotides of ‘C terminus of HSP70-Interacting Protein’ (CHIP). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of CHIP.

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Номер записи: 19

07-06-2012 дата публикации

Modified siNA

Номер: US20120142011A1

Автор: Alexander Azzawi, Eric fat Lader, Jie Kang, Peter Hahn, Wolfgang Bielke

Принадлежит: QIAGEN GmbH

The present invention pertains to the use of at least one abasic modification within the first 8 nucleotide positions of the 5′ region of the antisense strand of a small interfering nucleic acid (siNA) molecule for reducing off-target effects. Provided are suitable modified siNAs, compositions and methods for producing respective siNAs, as well as kits comprising respective siNAs.

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Номер записи: 20

07-06-2012 дата публикации

Treatment of 'iq motif containing gtpase activating protein' (iqgap) related diseases by inhibition of natural antisense transcript to iqgap

Номер: US20120142610A1

Автор: Carlos Coito, Joseph Collard, Olga Khorkova Sherman

Принадлежит: OPKO CURNA LLC

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of ‘IQ motif containing GTPase activating protein’ (IQGAP), in particular, by targeting natural antisense polynucleotides of ‘IQ motif containing GTPase activating protein’ (IQGAP). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of IQGAP.

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Номер записи: 21

07-06-2012 дата публикации

Sphingosine-bound siRNA

Номер: US20120142765A1

Автор: Ana Isabel JIMÉNEZ, Anna Avino, Clara Caminal, Gema Panizo, Ramon Eritja, Santiago Grijalvo, Tamara MARTÍNEZ

Принадлежит: Sylentis SA

The invention relates to novel oligomer analogues and their use in oligonucleotide-based therapies. More specifically, the invention concerns oligonucleotides carrying lipid molecules and their use as potential inhibitors of gene expression.

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Номер записи: 22

28-06-2012 дата публикации

Spinal muscular atrophy (sma) treatment via targeting of smn2 splice site inhibitory sequences

Номер: US20120165394A1

Автор: Elliot J. Androphy, Natalia N. Singh, Nirmal K. Singh, Ravindra N. Singh

Принадлежит: University of Massachusetts UMass

The present invention is directed to methods and compositions capable of blocking the inhibitory effect of a newly-identified intronic inhibitory sequence element, named ISS-N1 (for “intronic splicing silencer”), located in the SMN2 gene. The compositions and methods of the instant invention include oligonucleotide reagents (e.g., oligoribonucleotides) that effectively target the SMN2 ISS-N1 site in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the processed transcript. The ISS-N1 blocking agents of the invention cause elevated expression of SMN protein, thus compensating for the loss of SMN protein expression commonly observed in subjects with spinal muscular atrophy (SMA).

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Номер записи: 23

05-07-2012 дата публикации

In Vivo Polynucleotide Delivery Conjugates Having Enzyme Sensitive Linkages

Номер: US20120172412A1

Автор: Andrei V. Blokhin, Darren H. Wakefield, David B. Rozema, David L. Lewis, Eric A. Kitas, Guenther Ott, Hans Martin Mueller, Ingo Roehl, Jeffrey C. Carlson, Jon A. Wolff, Jonathan D. Benson, Kerstin Jahn-Hofmann, Peter Mohr, Philipp Hadwiger, Torsten Hoffmann

Принадлежит: Arrowhead Madison Inc

The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.

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Номер записи: 24

26-07-2012 дата публикации

Method for determining the presence and concentration of analytes using a nucleic acid ligand and rare earth elements

Номер: US20120190015A1

Автор: Gregory Allen Penner, Jorge Andres Cruz-Aguado

Принадлежит: Individual

The present invention relates to methods and an apparatus for determining the presence and concentration of an analyte in a sample and the binding of the analyte to a nucleic acid ligand that include measuring the fluorescence emitted by a rare earth element, i.e., terbium, in the presence of the analyte and the nucleic acid ligand. Specific embodiments include the use of terbium and nucleic acid ligands that specifically bind the mycotoxin ochratoxin. A, to detect and quantify ochratoxin A in, for example, food samples such as grain, wine, or beer. The detection of thrombin using terbium and a thrombin-specific nucleic acid ligand is also disclosed. The present invention also relates to a composition comprising a rare earth element as a cation that facilitates the binding of an analyte to a nucleic acid ligand of the analyte.

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Номер записи: 25

26-07-2012 дата публикации

Treatment of patients after stent implantation or balloon dilatation and drug eluting stents

Номер: US20120190580A1

Автор: Thomas Boettger, Thomas Braun

Принадлежит: Max Planck Gesellschaft zur Foerderung der Wissenschaften eV

The present invention relates to a nucleic acid molecule for use in the treatment or preventive treatment of a patient after stent implantation or balloon dilatation, wherein the nucleic acid molecule is selected from (a) a single-stranded nucleic acid molecule comprising or consisting of the sequence of SEQ ID NO: 1, 2, 3 or 4 or a sequence having at least 90% sequence identity to the sequence of SEQ ID NO: 1, 2, 3 or 4; (b) a hairpin RNA, wherein one of the regions forming the double-stranded portion of said hairpin RNA comprises or consists of the sequence of SEQ ID NO: 1, 2, 3 or 4 or a sequence having at least 90% sequence identity to the sequence of SEQ ID NO: 1, 2, 3 or 4; (c) an at least partially double-stranded RNA comprising two separate single strands, wherein a region within one of the strands, said region being located within the double-stranded portion of said double-stranded RNA, comprises or consists of the sequence of SEQ ID NO: 1, 2, 3 or 4 or a sequence having at least 90% sequence identity to the sequence of SEQ ID NO: 1, 2, 3 or 4; (d) a nucleic acid molecule encoding the nucleic acid molecule of (a) or the RNA (b); and (e) a nucleic acid molecule or a two nucleic acid molecules encoding the two separate single strands of the RNA of (c). The present invention also relates to a drug eluting stent comprising the nucleic acid molecule according to the invention.

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Номер записи: 26

16-08-2012 дата публикации

Bridged artificial nucleoside and nucleotide

Номер: US20120208991A1

Автор: Aiko Yahara, Masaru Nishida, Satoshi Obika, Tetsuya Kodama, Yoshiyuki Hari

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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Номер записи: 27

23-08-2012 дата публикации

Modulation of factor 7 expression

Номер: US20120214862A1

Автор: Brett P. Monia, Chenguang Zhao, Hong Zhang, Jeffrey R. Crosby, Susan M. Freier

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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Номер записи: 28

23-08-2012 дата публикации

Modified L-Nucleic Acid

Номер: US20120214868A1

Автор: Bernd Eschgfäller, Christian Lange, Sven Klussmann

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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Номер записи: 29

30-08-2012 дата публикации

Modified double-stranded polynucleotide

Номер: US20120220649A1

Автор: Makoto Koizumi, Yasuhide Hirota

Принадлежит: Daiichi Sankyo Co Ltd

The present invention provides a double-stranded polynucleotide having a sense strand polynucleotide consisting of a nucleotide sequence complementary to a target sequence in a target gene, and an antisense strand polynucleotide having a nucleotide sequence complementary to the sense strand polynucleotide, wherein an aryl or heteroaryl compound is bound to a phosphate group at the 5′-end of the antisense strand polynucleotide.

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Номер записи: 30

30-08-2012 дата публикации

Process for triphosphate oligonucleotide synthesis

Номер: US20120220761A1

Автор: François MORVAN, Françoise Debart, Ivan Zlatev, Jean-Jacques Vasseur, Muthiah Manoharan

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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Номер записи: 31

13-09-2012 дата публикации

Compositions and methods for prognosis and treatment of prostate cancer

Номер: US20120232124A1

Автор: Ayelet Chajut, Shai Rosenwald

Принадлежит: Rosetta Genomics Ltd

Described herein are compositions and methods for prognosis and treatment of prostate cancer patients. Specifically the invention relates to microRNA molecules associated with the prognosis of prostate cancer, as well as various nucleic acid molecules relating thereto or derived therefrom.

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Номер записи: 32

13-09-2012 дата публикации

Multi-targets interfering rna molecules and their applications

Номер: US20120232126A1

Автор: TieJun Li, York YuanYuan Zhu

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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Номер записи: 33

04-10-2012 дата публикации

Microrna as a cancer progression predictor and its use for treating cancer

Номер: US20120255043A1

Автор: Guang-Yuh Chiou, Shih-Hwa Chiou

Принадлежит: Taipei Veterans General Hospital

The present invention is based on the findings that a novel function for miR142-3p in the regulation of Sox2, adenylyl cyclase 9 (AC9), and CD133 expressions, and consequently the overall stemness of recurrent GBM cells as well as CSCs, and that miR142-3p modulated tumor-initiating properties in recurrent GBM. The present invention consequently supports the development of novel miRNA-based strategies for brain tumor treatment.

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Номер записи: 34

18-10-2012 дата публикации

Modular aptamer-regulated ribozymes

Номер: US20120263691A1

Автор: Christina D. Smolke, Katie Galloway, Maung Nyan Win

Принадлежит: California Institute of Technology CalTech

An extensible RNA-based framework for engineering ligand-controlled gene regulatory systems, called ribozyme switches, that exhibit tunable regulation, design modularity, and target specificity is provided. These switch platforms typically contain a sensor domain, comprised of an aptamer sequence, and an actuator domain, comprised of a hammerhead ribozyme sequence. A variety of modes of standardized information transmission between these domains can be employed, and this application demonstrates a mechanism that allows for the reliable and modular assembly of functioning synthetic hammerhead ribozyme switches and regulation of ribozyme activity in response to various effectors. In some embodiments aptamer-regulated cis-acting hammerhead ribozymes are provided.

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Номер записи: 35

01-11-2012 дата публикации

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

Номер: US20120277284A1

Автор: Eric E. Swayze, Robert A. MacLeod, Susan M. Freier, Youngsoo Kim

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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Номер записи: 36

22-11-2012 дата публикации

Modulation of glucagon receptor expression

Номер: US20120295958A1

Автор: Susan M. Freier

Принадлежит: ISIS PHARMACEUTICALS INC

Compounds, compositions and methods are provided for modulating the expression of glucagon receptor. The compositions comprise oligonucleotides, targeted to nucleic acid encoding glucagon receptor. Methods of using these compounds for modulation of glucagon receptor expression and for diagnosis and treatment of disease associated with expression of glucagon receptor are provided.

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Номер записи: 37

29-11-2012 дата публикации

Conjugates, particles, compositions, and related methods

Номер: US20120302622A1

Автор: Donald E. Bergstrom, Jungyeon Hwang, Oliver S. Fetzer, Patrick Lim Soo, Pei-Sze Ng, Scott Eliasof, Sonke Svenson

Принадлежит: Cerulean Pharma Inc

Particles and conjugates for delivering nucleic acid agents. Compositions containing the particles, the conjugates, or both. Methods of using the particles, the conjugates, and the compositions.

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Номер записи: 38

20-12-2012 дата публикации

Lna oligonucleotides and the treatment of cancer

Номер: US20120322848A1

Автор: Christoph Rosenbohm, Jens B. Hansen, Lene S. Kjaerulff, Majken Westergaard, Margit Wissenbach, Marlene Asklund

Принадлежит: Santaris Pharma As

The present disclosure concerns LNA oligonucleotides having a (sub)sequence of the general formula 5′-( Me C x )(T x ) Me C x A s A s t s C s C s a s t s g s g s Me C x A x ( G x )(c)-3′, and preferably of the general formula 5′- Me C x T x Me C x A s a s t s c s c s a s t s g s g s Me C x A x G x c-3′, wherein capital letters designate an LNA nucleotide analogue selected from β-D-oxy-LNA, β-D-thio-LNA, β-D-amino-LNA and α-L-oxy-LNA, small letters designate a deoxynucleotide, and underline designates either an LNA nucleotide analogue as defined above or a deoxynucleotide. Such LNA oligonucleotides exhibit surprisingly good properties with respect to inhibition of the expression of Survivin by means of an anti-sense mechanism, and thereby lead to reduction or inhibition of tumour development in vivo. The LNA oligonucleotides are superior to other LNA oligonucletides targeting Surviving mRNA measured by functional read outs such as apoptosis induction and proliferation inhibition, and is potent in down-regulating Survivin mRNA and protein in transfected cancer cell lines, and induce apoptosis in combination with Taxol superior compared to other LNA oligonucleotides.

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Номер записи: 39

27-12-2012 дата публикации

Therapeutic agent for fibroid lung

Номер: US20120328694A1

Автор: Rishu Takimoto, Yoshiro Niitsu

Принадлежит: Nitto Denko Corp

Disclosed are: a substance transfer carrier to an extracellular matrix-producing cell in the lung, which comprises a retinoid; a therapeutic agent for fibroid lung, which utilized the carrier; and a preparation kit of the therapeutic agent.

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Номер записи: 40

03-01-2013 дата публикации

Two-way, portable riboswitch mediated gene expression control device

Номер: US20130004980A1

Автор: Jian-Dong Huang, Ye Jin

Принадлежит: University of Hong Kong HKU

A regulatable gene expression construct comprising a nucleic acid molecule comprising a two-way riboswitch operably linked to a target sequence. Also provided is a library screening strategy for efficient creation of target-specific riboswitches. A theophylline-repressible and IPTG-inducible riboswitch device achieves portable control of gene expression control in a ‘two-way’ manner. The default state of target genes is ON; the targets are switched off by adding theophylline, and switched back to the ON-state by adding IPTG without changing growth medium. The riboswitch device regulates gene expression in a portable, adjustable, and two-way manner with a variety of scientific and biotechnological applications.

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Номер записи: 41

03-01-2013 дата публикации

Compositions and Methods for Inhibiting Gene Expression of Hepatitis B Virus

Номер: US20130005793A1

Автор: Daniel J. Chin, Jochen Deckert, Markus Hossbach, Matthias John

Принадлежит: Arrowhead Research Corp

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a Hepatitis B Virus gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by Hepatitis B Virus infection using said pharmaceutical composition; and methods for inhibiting the expression of a Hepatitis B Virus gene in a cell.

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Номер записи: 42

10-01-2013 дата публикации

Compositions And Methods For Inhibiting Expression Of GSK-3 Genes

Номер: US20130012572A1

Автор: Dinah Wen-Yee Sah, Gregory Hinkle

Принадлежит: Individual

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting Glycogen Synthase Kinase-3 (GSK-3), and methods of using the dsRNA to inhibit expression of GSK-3.

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Номер записи: 43

31-01-2013 дата публикации

Glycine riboswitches, methods for their use, and compositions for use with glycine riboswitches

Номер: US20130029342A1

Автор: Jeffrey Barrick, Maumita Mandal, Ronald R. Breaker

Принадлежит: YALE UNIVERSITY

Riboswitches are structural elements in mRNA that change state when bound by a trigger molecule, and are thus able to regulate gene expression. They can be dissected into two separate domains: one that selectively binds the target (aptamer domain) and another that influences genetic control (expression platform domain). Bacterial glycine riboswitches consist of two tandem aptamer domains which cooperatively bind glycine to regulate the expression of downstream genes. These natural switches are targets for antibiotics and other small molecule therapies. Modified versions of these natural riboswitches can be employed as designer genetic switches that are controlled by specific effector compounds. Disclosed are isolated and recombinant riboswitches, and compositions and methods for selecting and identifying compounds that can activate, inactivate, or block a riboswitch.

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Номер записи: 44

07-02-2013 дата публикации

Synthetic nanostructures including nucleic acids and/or other entities

Номер: US20130034599A1

Автор: Andrea Luthi, C. Shad Thaxton, Chad A. Mirkin, David M. Leander, Kaylin M. MCMAHON, Raja Kannan Mutharasan, Sushant Tripathy

Принадлежит: Northwestern University

Articles, compositions, kits, and methods relating to nanostructures, including synthetic nanostructures, are provided. Certain embodiments described herein include structures having a core-shell type arrangement; for instance, a nanostructure core may be surrounded by a shell including a material, such as a lipid bilayer, and may include other components such as oligonucleotides. In some embodiments, the structures, when introduced into a subject, can be used to deliver nucleic acids and/or can regulate gene expression. Accordingly, the structures described herein may be used to diagnose, prevent, treat or manage certain diseases or bodily conditions. In some cases, the structures are both a therapeutic agent and a diagnostic agent.

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Номер записи: 45

07-02-2013 дата публикации

Lipid formulated dsrna targeting the pcsk9 gene

Номер: US20130035371A1

Автор: Akin Akinc, Gregory Hinkle, Kevin Fitzgerald, Stuart Milstein

Принадлежит: Individual

This invention relates to composition and methods using lipid formulated siRNA targeted to a PCSK9 gene.

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Номер записи: 46

14-02-2013 дата публикации

Aptamer to fgf2 and use thereof

Номер: US20130039855A1

Автор: Akira Ishiguro, Maiko Sakamoto, Yoshikazu Nakamura

Принадлежит: Ribomic Inc

Provided are an aptamer having an inhibitory activity on FGF2; a complex containing an aptamer having a binding activity or an inhibitory activity on FGF2, and a functional substance (e.g., affinity substance, labeling substance, enzyme, drug delivery vehicle, or drug and the like); a medicament, diagnostic reagent or label containing an aptamer having a binding activity or an inhibitory activity on FGF2, or a complex containing said aptamer and a functional substance; and the like.

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Номер записи: 47

14-02-2013 дата публикации

Mir-150 for the treatment of blood disorders

Номер: US20130039895A1

Автор: Benjamin Ebert, David Scadden, Jun Lu, Shangqin Guo, Todd Golub

Принадлежит: Dana Farber Cancer Institute Inc, General Hospital Corp, Massachusetts Institute of Technology

The invention provides methods of treating certain blood related disorders, in particular, thrombocytopenia and anemia comprising increasing miR-150 expression or inhibiting miR-150 in progenitor cells respectively.

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Номер записи: 48

21-02-2013 дата публикации

Treatment of metastatic tumors

Номер: US20130045163A1

Автор: Abdellah Sentissi, Alison O'Neill, Douglas B. Jacoby, E. Michael Egan, Kamala Kesavan

Принадлежит: Morphotek Inc

The present invention is directed to methods and methods for the treatment, inhibition and/or reduction, and detection of metastatic tumors. In some embodiments, the inventive methods include systemic (e.g., intravenous) administration of a chlorotoxin agent that may or may not be labeled. In some embodiments, the inventive methods allow treatment, inhibition and/or reduction, and detection of metastases in the brain. In some embodiments, neovascularization is inhibited and/or newly formed vessels are caused to regress.

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Номер записи: 49

21-03-2013 дата публикации

Treatment of methionine sulfoxide reductase a (msra) related diseases by inhibition of natural antisense transcript to msra

Номер: US20130072546A1

Автор: Joseph Collard, Olga Khorkova Sherman

Принадлежит: Curna Inc

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Methionine Sulfoxide Reductase A (MSRA), in particular, by targeting natural antisense polynucleotides of Methionine Sulfoxide Reductase A (MSRA). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of MSRA.

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Номер записи: 50

21-03-2013 дата публикации

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

Номер: US20130072671A1

Автор: Judith C. Van Deutekom

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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Номер записи: 51

04-04-2013 дата публикации

Protein complementation regulators

Номер: US20130085095A1

Автор: Paul Terence Toran

Принадлежит: Boston University

The present invention relates to protein complementation regulators and methods for reducing target-independent interaction of protein complementation molecules.

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Номер записи: 52

02-05-2013 дата публикации

Methods and compositions for the specific inhibition of beta-catenin by double-stranded rna

Номер: US20130109740A1

Автор: Bob D. Brown, Henryk T. Dudek

Принадлежит: Dicerna Pharmaceuticals Inc

This invention relates to compounds, compositions, and methods useful for reducing β-catenin target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

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Номер записи: 53

16-05-2013 дата публикации

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

Номер: US20130121988A1

Автор: Birgit Scheel, Ingmar Hoerr, Jochen Probst, Thomas Ketterer

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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Номер записи: 54

30-05-2013 дата публикации

Compositions and Methods for Gene Silencing

Номер: US20130137749A1

Автор: Rafal Goraczniak, Samuel Ian Gunderson

Принадлежит: Rutgers State University of New Jersey, Silagene Inc

Compositions and methods for modulating the expression of a protein of interest are provided.

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Номер записи: 55

30-05-2013 дата публикации

Treatment of glial cell derived neurotrophic factor (gdnf) related diseases by inhibition of natural antisense transcript to gdnf

Номер: US20130137751A1

Автор: Carlos Coito, Joseph Collard, Olga Khorkova Sherman

Принадлежит: Curna Inc

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Glial cell derived neurotrophic factor (GDNF), in particular, by targeting natural antisense polynucleotides of Glial cell derived neurotrophic factor (GDNF). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of GDNF.

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Номер записи: 56

06-06-2013 дата публикации

Compositions for inhibiting gene expression and uses thereof

Номер: US20130142778A1

Автор: Ekambar Kandimalla, Ireneusz Nowak, Mallikarjuna Putta, Michael Reardon, Nicola LaMonica, Sudhir Agrawal, Tao Lan, Weiwen Jiang

Принадлежит: Idera Pharmaceuticals Inc

The inventors have examined the means for providing more efficacious miRNA blocking compounds. The inventors have discovered new structural features that surprisingly improve the efficacy of miRNA blocking molecules. These features include the presence of multiple 3′ ends and a linker at the 5′ ends. Surprisingly, these features improve the efficacy of the gene expression blocking compounds in a manner that decreases the compound's biologic instability. Even more surprisingly, this effect has been found to be applicable to both DNA and RNA oligonucleotide-based compounds and to have application in traditional antisense and RNAi technology.

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Номер записи: 57

06-06-2013 дата публикации

Therapeutic compositions

Номер: US20130144048A1

Автор: David Bumcrot, Kallanthottathil G. Rajeev, Muthiah Manoharan

Принадлежит: Alnylam Pharmaceuticals Inc

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

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Номер записи: 58

20-06-2013 дата публикации

Methods for identifying compounds that modulate lisch-like protein or c1orf32 protein activity and methods of use

Номер: US20130160150A1

Автор: Charles LeDuc, Marija Dokmanovic-Chouinard, Rudolph L. Leibel, Stuart G. Fischer, Wendy K. Chung

Принадлежит: Columbia University of New York

The invention provides methods for reducing diabetes susceptibility in a subject and methods for increasing the expression of LL or CLORF32 in a subject. The invention further provides a method for identifying an agent which modulates expression of an Ll RNA or Clorf32 RNA comprising contacting a cell with an agent; determining expression of the Ll RNA or Clorf32 RNA in the presence and the absence of the agent; and comparing expression of the Ll RNA or Clorf32 RNA in the presence and the absence of the agent, wherein a change in the expression of the Ll RNA or Clorf32 RNA in the presence of the agent is indicative of an agent which modulates the level of expression of the RNA.

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Номер записи: 59

04-07-2013 дата публикации

Method for selective oligonucleotide modification

Номер: US20130172238A1

Автор: Andreas Mitsch, Anneliese Schneider, Bernd Betzler, Frank Jaschinski, Karl-Hermann Schlingensiepen

Принадлежит: Individual

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

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Номер записи: 60

04-07-2013 дата публикации

Selective inhibition of polyglutamine protein expression

Номер: US20130172399A1

Автор: David R. Corey, Dinah W.Y. Sah, Jiaxin Hu

Принадлежит: Individual

The present invention relates to the selective inhibition of protein expression of CAG repeat-related disease proteins such as Huntingtin Disease Protein and Ataxin-3 using double-stranded RNAs and nucleic acid analogs. Chemically-modified RNAs having at least one mismatch as compared to the target CAG repeat sequence are specifically contemplated.

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Номер записи: 61

11-07-2013 дата публикации

Mirna expression in allergic disease

Номер: US20130177624A1

Автор: Arash Olyie Naghavi, David Brian Corry, Farrah Kheradmand, Preethi Gunaratne, Sumanth Polikepahad

Принадлежит: Arash Olyie Naghavi, David Brian Corry, Farrah Kheradmand, Preethi Gunaratne, Sumanth Polikepahad

Disclosed are methods for detecting an allergic lung disease that involve assessing the level of one or more microRNAs (miRNAs) in a biological sample, wherein the level of the one or more miRNAs in the biological sample compared to a reference level of the one or more miRNAs is indicative of allergic lung disease. Also disclosed are methods for the treatment or prevention of inflammatory or allergic lung disease that involve administration of a let-7 miRNA inhibitor as set forth herein, as well as biochips and kits that can be applied in the methods of the present invention.

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Номер записи: 62

18-07-2013 дата публикации

Ligand-conjugated monomers

Номер: US20130184328A1

Автор: Kallanthottathil G. Rajeev, Muthiah Manoharan, Venkitasamy Kesavan

Принадлежит: Alnylam Pharmaceuticals Inc

This invention relates composition and methods for making and using chemically modified oligonucleotides agents for inhibiting gene expression.

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Номер записи: 63

01-08-2013 дата публикации

ENHANCEMENT OF siRNA SILENCING ACTIVITY USING UNIVERSAL BASES OR MISMATCHES IN THE SENSE STRAND

Номер: US20130196434A1

Автор: Haripriya Addepalli, Martin Maier, Muthiah Manoharan

Принадлежит: Alnylam Pharmaceuticals Inc

One aspect of the present invention relates to a double stranded nucleic acid useful as an siRNA, that has a sense strand and an antisense strand relative to a target nucleic acid, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one nucleoside comprising a non-natural nucleobase. Another aspect of the invention relates to a method of gene silencing, comprising administering to a mammal in need thereof a therapeutically effective amount of a double-stranded oligonucleotides containing a sense strand and an antisense strand, where the sense strand contains one or more modified nucleobases, or one or more mismatch base pairings with the antisense strand.

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Номер записи: 64

08-08-2013 дата публикации

Asymmetric biofunctional silyl monomers and particles thereof as prodrugs and delivery vehicles for pharmaceutical, chemical and biological agents

Номер: US20130203675A1

Автор: Ashish Pandya, Joseph M. Desimone, Mary Napier, Matthew Finniss, Matthew Parrott

Принадлежит: Individual

Asymmetric bifunctional silyl (ABS) monomers comprising covalently linked pharmaceutical, chemical and biological agents are described. These agents can also be covalently bound via the silyl group to delivery vehicles for delivering the agents to desired targets or areas. Also described are delivery vehicles which contain ABS monomers comprising covalently linked agents and to vehicles that are covalently linked to the ABS monomers. The silyl modifications described herein can modify properties of the agents and vehicles, thereby providing desired solubility, stability, hydrophobicity and targeting.

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Номер записи: 65

22-08-2013 дата публикации

Preventive or therapeutic agent for fibrosis

Номер: US20130217754A1

Автор: Ayako Fukuda, Esteban C. Gabazza, Hidekazu Toyobuku, Tetsu Kobayashi, Tetsuya Hasegawa

Принадлежит: Mie University NUC, Otsuka Pharmaceutical Co Ltd

Provided is siRNA effective for the treatment of fibrosis and a pharmaceutical containing the siRNA. An siRNA having a full length of 30 or fewer nucleotides and targeting a sequence consisting of 17 to 23 consecutive bases selected from the group consisting of bases at positions 1285 to 1318, bases at positions 1398 to 1418, bases at positions 1434 to 1463, bases at positions 1548 to 1579, bases at positions 1608 to 1628, bases at positions 1700 to 1726, bases at positions 1778 to 1798, bases at positions 1806 to 1826, and bases at positions 1887 to 1907 of SEQ ID NO: 1.

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Номер записи: 66

29-08-2013 дата публикации

Micrornas that regulate muscle cell proliferation and differentiation

Номер: US20130225658A1

Автор: Da-Zhi Wang, Jianfu Chen

Принадлежит: UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL

The presently disclosed subject matter provides methods and compositions for modulating gene expression in myocytes. Also provided are cells comprising the compositions of the presently disclosed subject matter.

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Номер записи: 67

29-08-2013 дата публикации

Modulation of nuclear-retained rna

Номер: US20130225659A1

Автор: C. Frank Bennett

Принадлежит: ISIS PHARMACEUTICALS INC

Provided herein are methods, compounds, and compositions for reducing expression of a nrRNA in an animal. Also provided herein are methods, compounds, and compositions for treating, ameliorating, delaying or reducing a symptom of a disease or disorder associated with a nuclear-retained RNA in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a disease or condition associated with a nuclear-retained RNA, or a symptom thereof.

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Номер записи: 68

05-09-2013 дата публикации

Sequence specific double-stranded dna/rna binding compounds and uses thereof

Номер: US20130231480A1

Автор: Anwar Rayan, Mizied Falah

Принадлежит: GENEARREST LTD

The present invention provides specific double-stranded DNA/RNA binding compounds having a polymeric structure, which are in fact, triplex forming molecules capable of binding tightly and specifically to predetermined sequences in the major groove of double stranded nucleic acid molecules; as well as pharmaceutical compositions comprising thereof. The triplex forming molecules and the pharmaceutical compositions of the invention can be used for various therapeutic applications such as site-specific modulation of gene expression, targeting of DNA or RNA damage, and gene knockout, as well as for diagnostic applications in vitro.

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Номер записи: 69

12-09-2013 дата публикации

Aptamer therapeutics useful in the treatment of complement-related disorders

Номер: US20130237589A1

Автор: Charles Wilson, Claude Benedict, David Epstein, Dilara McCauley, James Rottman, Jeffrey Kurz, Markus Kurz, Thomas Greene McCauley

Принадлежит: ARCHEMIX LLC

The invention provides nucleic acid therapeutics and methods for using these nucleic acid therapeutics in the treatment of complement-related disorders.

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Номер записи: 70

12-09-2013 дата публикации

Vascular therapeutics

Номер: US20130237696A1

Автор: Levon M. Khachigian

Принадлежит: NEWSOUTH INNOVATIONS PTY LTD

The present invention provides a method of preventing or reducing restenosis, neointima formation, graft failure, atherosclerosis, angiogenesis and/or solid tumour growth in a subject. The method comprises administering to the subject a prophylactically effective dose of a nucleic acid which decreases the level of c-Jun mRNA, c-Jun mRNA translation or nuclear accumulation or activity of c-Jun. It is preferred that the nucleic acid is a DNAzymc that targets c-Jun mRNA.

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Номер записи: 71

26-09-2013 дата публикации

Novel single chemical entities and methods for delivery of oligonucleotides

Номер: US20130253168A1

Автор: Anthony W. Shaw, Daniel Zewge, David M. Tellers, Francis Gosselin, Steven L. Colletti, Thomas J. Tucker, Vasant R. Jadhav, Yu Yuan

Принадлежит: Individual

In an embodiment the instant invention discloses a modular composition comprising 1) an oligonueleotide; 2) one or more linkers, which may be the same or different, selected from Table 1, wherein the linkers are attached to the oligonucleotide at the 2′-position of the ribose rings and/or the terminal 3′- and/or 5′-positions of the oligonucleotide; 3) optionally, one or more peptides, which may be the same or different, selected from SEQ ID NOs: 1-59, wherein the peptides are attached to the linkers; and optionally one or more lipids, solubilizing groups and/or targeting ligands attached to the oligonucleotide.

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Номер записи: 72

26-09-2013 дата публикации

Antisense oligonucleotides for inducing exon skipping and methods of use thereof

Номер: US20130253180A1

Автор: Graham McClorey, Stephen Donald Wilton, Sue Fletcher

Принадлежит: University of Western Australia

Antisense molecules capable of binding to a selected target site in the dystrophin gene to induce exon skipping are described.

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Номер записи: 73

10-10-2013 дата публикации

Gene Silencing by Single-Stranded Polynucleotides

Номер: US20130267577A1

Автор: Gretchen M. Unger

Принадлежит: GeneSegues Inc

The present invention relates to compositions and methods for concurrently activating antisense and double-stranded RNase (dsRNase) mechanisms for inhibiting expression of a targeted gene, by delivering a single stranded bifunctional chimeric DNA/RNA oligonucleotide optimized for siRNA activity as well as antisense activity, into the nucleus of a target cell.

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Номер записи: 74

10-10-2013 дата публикации

Immune regulatory oligonucleotide (iro) compounds to modulate toll-like receptor based immune response

Номер: US20130267583A1

Автор: Daqing Wang, Dong Yu, Ekambar R. Kandimalla, FuGang Zhu, Lakshmi Bhagat, Sudhir Agrawal, Yukui Li

Принадлежит: Idera Pharmaceuticals Inc

The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.

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Номер записи: 75

24-10-2013 дата публикации

Compositions and methods for inhibiting expression of the alas1 gene

Номер: US20130281511A1

Автор: Brian Bettencourt, Kevin Fitzgerald, Makiko Yasuda, Robert J. Desnick, William Querbes

Принадлежит: Individual

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ALAS1 gene, and methods of using such dsRNA compositions to alter (e.g., inhibit) expression of ALAS1.

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Номер записи: 76

12-12-2013 дата публикации

Methods for modulating factor 12 expression

Номер: US20130331434A1

Автор: Brett P. Monia, Jeffrey R. Crosby, Robert A. MacLeod

Принадлежит: ISIS PHARMACEUTICALS INC

Disclosed herein are methods for decreasing Factor 12 and treating or preventing thromboembolic conditions in an individual in need thereof. Examples of disease conditions that can be ameliorated with the administration of antisense compounds targeted to Factor 12 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and mesenteric thrombosis. Methods for inhibiting Factor 12 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism.

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Номер записи: 77

12-12-2013 дата публикации

Antisense oligonucleotides for inducing exon skipping and methods of use thereof

Номер: US20130331438A1

Автор: Graham McClorey, Stephen Donald Wilton, Sue Fletcher

Принадлежит: University of Western Australia

An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

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Номер записи: 78

19-12-2013 дата публикации

Composition and method for oligonucleotide delivery

Номер: US20130338215A1

Автор: Judy Lieberman, Lee Adam Wheeler

Принадлежит: Childrens Medical Center Corp

The invention provides aptamer-gene modulator conjugates, where the aptamer and the gene modulator are linked together. The invention further provides a method for cell-specific delivery of gene modulators to hard to transfect cells such as CD4+ cell.

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Номер записи: 79

02-01-2014 дата публикации

Chimeric oligomeric compounds for modulation of splicing

Номер: US20140005374A1

Автор: C. Frank Bennett, Casey C. Kopczynski, Nicholas M. Dean, Ryszard M. Kole

Принадлежит: ISIS PHARMACEUTICALS INC, Sarepta Therapeutics Inc

Disclosed herein are compounds, compositions and methods for modulating splicing of a selected target mRNA. Further provided are uses of the disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders. Methods of enhancing cellular uptake, modulating tissue distribution and enhancing pharmacological activity of RNase H-independent antisense oligonucleotides are also provided.

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Номер записи: 80

09-01-2014 дата публикации

Chimeric molecules to modulate gene expression

Номер: US20140011977A1

Автор: Adrian R. Krainer, Luca Cartegni

Принадлежит: COLD SPRING HARBOR LABORATORY

The present invention provides a chimeric molecule including a base-pairing segment that binds specifically to a single-stranded nucleic acid molecule; and a moiety that modulates splicing or translation. The invention also provides a chimeric molecule including a base-pairing segment that binds specifically to a double-stranded nucleic acid molecule; and a peptide that modulates transcription, wherein the peptide comprises up to about one hundred amino acid residues.

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Номер записи: 81

16-01-2014 дата публикации

LOW DENSITY LIPOPROTEIN RECEPTOR-MEDIATED siRNA DELIVERY

Номер: US20140018296A1

Автор: Jon E. Chatterton

Принадлежит: Alcon Research LLC

The invention provides interfering RNA molecule-ligand conjugates useful as a delivery system for delivering interfering RNA molecules to a cell in vitro or in vivo. The conjugates comprise a ligand that can bind to a low density lipoprotein receptor (LDLR) or LDLR family member. Therapeutic uses for the conjugates are also provided.

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Номер записи: 82

23-01-2014 дата публикации

Methods for treating progeroid laminopathies using oligonucleotide analogues targeting human lmna

Номер: US20140024698A1

Автор: Francis S. Collins, Kan CAO, Michael R. Erdos, Ryszard Kole

Принадлежит: Sarepta Therapeutics Inc, University of Maryland at Baltimore, US Department of Health and Human Services

Provided are methods of treatment in subjects having progeroid diseases and related conditions which rely upon LMNA-targeted antisense oligonucleotides for reducing expression of one or more aberrantly spliced LMNA mRNA isoforms that encode progerin.

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Номер записи: 83

30-01-2014 дата публикации

Methods for treating androgen receptor dependent disorders including cancers

Номер: US20140031409A1

Автор: Jesper Worm, Yixian Zhang

Принадлежит: Santaris Pharma As

The invention provides the combination use of antisense oligomers targeting androgen receptor mRNA and androgen receptor binding inhibitors that reduce androgen receptor activity for the treatment of androgen receptor related medical disorders, such as cancers, particularly prostate cancers and breast cancers.

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Номер записи: 84

30-01-2014 дата публикации

Methods and compositions involving mirna and mirna inhibitor molecules

Номер: US20140031415A1

Автор: Angie Cheng, David Brown, Dmitriy Ovcharenko, Eric Devroe, Kevin Kelnar, Lance Ford, Mike Byrom, Rich Jarvis

Принадлежит: Asuragen Inc

The present invention concerns methods and compositions for introducing miRNA activity or function into cells using synthetic nucleic acid molecules. Moreover, the present invention concerns methods and compositions for identifying miRNAs with specific cellular functions that are relevant to therapeutic, diagnostic, and prognostic applications wherein synthetic miRNAs and/or miRNA inhibitors are used in library screening assays.

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Номер записи: 85

13-02-2014 дата публикации

G-quadruplex binding assays and compounds therefor

Номер: US20140045726A1

Автор: Lesley Davenport

Принадлежит: Individual

The present invention provides methods for assaying binding of compounds to G-quadruplex structures. Also provided are methods for screening candidate compounds for use as modulators of G-quadruplex activity, and methods for screening candidate compounds for telomerase inhibitory activity. The invention further provides novel compounds useful in the assays of the invention.

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Номер записи: 86

20-02-2014 дата публикации

Methods targeting mir-128 for regulating cholesterol/lipid metabolism

Номер: US20140051746A1

Автор: Anders M. NAAR, Seyed Hani Najafi-Shoushtari

Принадлежит: General Hospital Corp

Methods for targeting microRNA 128 (miR-128) for regulating cholesterol/lipid metabolism and insulin sensitivity.

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Номер записи: 87

06-03-2014 дата публикации

Stacking nucleic acid and methods for use thereof

Номер: US20140065676A1

Автор: Gorm Lisby, Nikolaj Dam Mikkelsen, Uffe Vest Schneider

Принадлежит: Quantibact AS

The present invention provides a novel modified oligonucleotide monomer useful in molecular biological techniques such as capture and/or detection of nucleic acids, amplification of nucleic acids and sequencing of nucleic acids. The modified oligonucleotide monomer comprises an intercalator that can intercalate into an antiparallel duplex from the major groove.

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Номер записи: 88

06-03-2014 дата публикации

Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription

Номер: US20140068797A1

Автор: Emmanuelle CHARPENTIER, James Harrison DOUDNA CATE, Jennifer A. DOUDNA, Krzysztof CHYLINSKI, Lei Qi, Martin Jinek, Wendell Lim

Принадлежит: Universitaet Wien, UNIVERSITY OF CALIFORNIA

The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms.

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Номер записи: 89

20-03-2014 дата публикации

Antisense oligonucleotides for inducing exon skipping and methods of use thereof

Номер: US20140080898A1

Автор: Graham McClorey, Stephen Donald Wilton, Sue Fletcher

Принадлежит: University of Western Australia

Antisense molecules capable of binding to a selected target site in the dystrophin gene to induce exon skipping are described.

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Номер записи: 90

27-03-2014 дата публикации

Compounds and methods for altering activin receptor-like kinase signaling

Номер: US20140088174A1

Автор: Adriana Marie Rus, Dwi Utami KEMALADEWI, Peter Abraham Christiaan "T Hoen, Peter Ten Duke, Wilhelmus Martinus Hendrikus HOOGAARS

Принадлежит: Leids Universitair Medisch Centrum LUMC

Described are compounds and methods useful in the promotion of muscle growth, the treatment of muscle loss or insufficient muscle growth, and the treatment of fibrotic conditions.

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Номер записи: 91

03-01-2019 дата публикации

COMPOSITIONS AND METHODS FOR INHIBITING HMGB1 EXPRESSION

Номер: US20190000870A1

Автор: Abrams Marc, CHOPDA Girish, PARK Jihye

Принадлежит: Dicerna Pharmaceuticals, Inc.

This disclosure relates to oligonucleotides, compositions and methods useful for reducing HMGB1 expression, particularly in hepatocytes. Disclosed oligonucleotides for the reduction of HMGB1 expression may be double-stranded or single-stranded, and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of HMGB1 expression may also be designed to include targeting ligands to target a particular cell or organ, such as the hepatocytes of the liver, and may be used to treat liver fibrosis and related conditions. 1. An oligonucleotide for reducing expression of HMGB1 , the oligonucleotide comprising an antisense strand of 15 to 30 nucleotides in length , wherein the antisense strand has a region of complementarity to HMGB1 that is complementary to at least 15 contiguous nucleotides of a sequence as set forth in SEQ ID NO: 374-381 , 193-272 , and 363-365.2. The oligonucleotide of claim 1 , wherein the antisense strand is 19 to 27 nucleotides in length.3. The oligonucleotide of claim 1 , wherein the antisense strand is 21 to 27 nucleotides in length.4. The oligonucleotide of claim 1 , wherein the region of complementarity is complementary to at least 15 contiguous nucleotides of a sequence as set forth in SEQ ID NO: 193-272 or 363-365.5. The oligonucleotide of claim 1 , further comprising a sense strand of 15 to 50 nucleotides in length claim 1 , wherein the sense strand forms a duplex region with the antisense strand.6. The oligonucleotide of claim 1 , wherein the region of complementarity with HMGB1 is complementary to at least 19 contiguous nucleotides of a sequence as set forth in SEQ ID NO: 374-381.7. The oligonucleotide of claim 1 , wherein the region of complementarity with HMGB1 is complementary to at least 19 contiguous nucleotides of a sequence as set forth in SEQ ID NO: 193-272 or 363-365.8. The oligonucleotide of claim 5 , wherein the sense strand comprises a ...

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Номер записи: 92

07-01-2021 дата публикации

NOVEL FATTY ACIDS AND THEIR USE IN CONJUGATION TO BIOMOLECULES

Номер: US20210000964A1

Автор: BARNES David Weninger, BOSE Avirup, BRUCE Alexandra Marshall, DUTTAROY Alokesh, IBEBUNJO Chikwendu, KANTER Aaron, KIRMAN Louise Clare, LOU Changgang, USERA Aimee Richardson, YAMADA Ken, Yuan Jun, ZECRI Frederic

Принадлежит:

The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3: 124-. (canceled)26. The compound according to claim 25 , or an amide claim 25 , ester or pharmaceutically acceptable salt thereof claim 25 , wherein the compound is of Formula A1 wherein at least one of Rand Ris COH.29. A peptide selected from MH(199-308)hGDF15 (SEQ ID NO: 4) claim 25 , MHA(200-308)hGDF15 (SEQ ID NO: 6) claim 25 , AHA(200-308)hGDF15 (SEQ ID NO: 7) claim 25 , AH(199-308)hGDF15 (SEQ ID NO: 5) claim 25 , MHHHHHHM-hGDF15 (SEQ ID NO: 2) and MHHHHHH-hGDF15 (SEQ ID NO: 1). This application is a divisional application of U.S. application Ser. No. 15/985,060, filed on May 21, 2018, now allowed, which is a divisional of Ser. No. 14/738,272, filed on Jun. 12, 2015, now U.S. Pat. No. 10,588,980, which claims priority to, and the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Application No. 62/107,016, filed Jan. 23, 2015, U.S. Provisional Application No. 62/082,327, filed on Nov. 20, 2014, and U.S. Provisional Application No. 62/015,862 filed on Jun. 23, 2014, the entire contents of each of which are incorporated herein by reference in their entireties.The contents of the text file named “PAT056274-US-DIV02_Sequence Listing_ST25.txt,” which was created on May 26, 2020 and is 33 KB in size, are hereby incorporated by reference in their entireties.The present invention relates to novel conjugates of GDF15 which have improved half-life and duration of action, method of making them and using them. The invention further relates to novel fatty acids and their use in extending the half-life of biomolecules via conjugation.Peptides and proteins are widely used in medical practice, and since they can be produced by recombinant DNA technology it can be expected that their importance will increase also in the years to come. The number of known endogenous peptides and proteins with interesting biological ...

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Номер записи: 93

02-01-2020 дата публикации

MODULATION OF FACTOR 11 EXPRESSION

Номер: US20200000839A1

Автор: Crosby Jeffrey R., Freier Susan M., Monia Brett P., Siwkowski Andrew M., ZHANG Hong, Zhao Chenguang

Принадлежит: Ionis Pharmaceuticals, Inc.

Disclosed herein are antisense compounds and methods for decreasing Factor 11 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 11 include thrombosis, embolism, and thromboembolism, such as, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke. Antisense compounds targeting Factor 11 can also be used as a prophylactic treatment to prevent individuals at risk for thrombosis and embolism. 154.-. (canceled)55. A compound comprising a modified oligonucleotide , wherein the modified oligonucleotide consists of 12 to 30 linked nucleosides , and wherein at least 12 linked nucleosides of the modified oligonucleotide has a nucleobase sequence of SEQ ID NO: 141.56. The compound of claim 55 , wherein the modified oligonucleotide has a nucleobase sequence that is at least 85% complementary to any of the nucleobase sequences of SEQ ID NO: 1 or SEQ ID NO: 2 when measured across the entire nucleobase sequence of the modified oligonucleotide.57. The compound of claim 55 , wherein the modified oligonucleotide consists of a single stranded modified oligonucleotide.58. The compound of claim 55 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage.59. The compound of claim 58 , wherein the at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage.60. The compound of claim 55 , wherein the modified oligonucleotide comprises at least one modified sugar.61. The compound of claim 60 , wherein the at least one modified sugar comprises a 2′-O-methoxyethyl group.62. The compound of claim 60 , wherein the at least one modified sugar comprises a 2′-O—CHgroup.63. The compound of claim 60 , wherein the at least one modified sugar is a bicyclic sugar.64. The compound of claim 63 , wherein the bicyclic sugar comprises a 4′-(CH)—O-2′ bridge.65. ...

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Номер записи: 94

07-01-2016 дата публикации

Nanoparticles stabilized with nitrophenylboronic acid compositions

Номер: US20160000934A1

Автор: Han Han, Mark E. Davis

Принадлежит: California Inst Of Techn

Described herein are polymer conjugates comprising a polymer containing a polyol coupled to a polymer containing a nitroboronic acid.

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Номер записи: 95

05-01-2017 дата публикации

LIPID FORMULATED DSRNA TARGETING THE PCSK9 GENE

Номер: US20170000815A1

Автор: Akinc Akin, Fitzgerald Kevin, Hinkle Gregory, Milstein Stuart

Принадлежит:

This invention relates to composition and methods using lipid formulated siRNA targeted to a PCSK9 gene. 1. A composition comprising a nucleic acid lipid particle comprising a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a human PCSK9 gene in a cell , wherein:the nucleic acid lipid particle comprises a lipid formulation comprising 45-65 mol % of a cationic lipid, 5 mol % to about 10 mol %, of a non-cationic lipid, 25-40 mol % of a sterol, and 0.5-5 mol % of a PEG or PEG-modified lipid,the dsRNA consists of a sense strand and an antisense strand, and the sense strand comprises a first sequence and the antisense strand comprises a second sequence complementary to at least 15 contiguous nucleotides of a nucleotide sequence of a target sequence of a dsRNA found in Table 1a, Table 2a, Table 5a, Table 6, Table 7, Table 8,wherein the first sequence is complementary to the second sequence and wherein the dsRNA is between 15 and 30 base pairs in length.2. The composition of claim 1 , wherein the cationic lipid comprises MC3 (((6Z claim 1 ,9Z claim 1 ,28Z claim 1 ,31Z)-heptatriaconta-6 claim 1 ,9 claim 1 ,28 claim 1 ,31-tetraen-19-yl 4-(dimethylamino)butanoate).49.-. (canceled)10. The composition of claim 1 , wherein the sense strand comprises SEQ ID NO:1227 and the antisense strand comprises SEQ ID NO:1228.11. (canceled)12. (canceled)13. The composition of claim 1 , wherein the dsRNA comprises at least one modified nucleotide.14. The composition of claim 13 , wherein the modified nucleotide is chosen from the group of: a 2′-O-methyl modified nucleotide claim 13 , a nucleotide comprising a 5′-phosphorothioate group claim 13 , and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group.15. The composition of claim 13 , wherein the modified nucleotide is chosen from the group of: a 2′-deoxy-2′-fluoro modified nucleotide claim 13 , a 2′-deoxy-modified nucleotide claim 13 , a locked nucleotide claim 13 , an ...

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Номер записи: 96

06-01-2022 дата публикации

CARBORHODAMINE COMPOUNDS AND METHODS OF PREPARATION THEREOF

Номер: US20220002549A1

Автор: Lukhtanov Eugeny A.

Принадлежит: ELITechGroup, Inc.

The carborhodamine dyes disclosed herein are novel reagents suitable for automated incorporation of carborhodamine dyes into oligonucleotides that can be used in detection methods for nucleic acid targets. This disclosure provides an efficient and simple process for the preparation of carborhodamine compounds and introduces previously unknown reagents for the automated synthesis of oligonucleotide-carborhodamine conjugates. 2. The method of claim 1 , wherein the solvent is 1 claim 1 ,2-dichloroethane and the Lewis acid is aluminum chloride.3. The method of claim 1 , wherein one or more hydrocarbon hydrogens of Ror Ris replaced with a linking group.4. The method of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rform one or more 4- to 7-member ring systems by bridging between one or more of Rwith R claim 1 , Rwith R claim 1 , Rwith R claim 1 , Rwith R claim 1 , Rwith R claim 1 , and Rwith R.5. The method of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rform one or more 4- to 7-member ring systems linked to one or more further 4- to 7-member ring systems claim 1 , and wherein the one or more further 4- to 7-member ring systems comprise up to 3 double bonds.6. The method of claim 5 , wherein the one or more further 4- to 7-member ring systems comprise heteroatoms.7. The method of claim 1 , wherein R claim 1 , R claim 1 , Rand Rform one or more 4- to 7-member ring systems by bridging between one or more of Rwith R claim 1 , Rwith R claim 1 , and Rwith R.8. The method of claim 1 , wherein R claim 1 , R claim 1 , Rand Rform one or more 4- to 7-member ring systems linked to one or more further 4- to 7-member ring systems claim 1 , and wherein the one or more further 4- to 7-member ring systems comprise up to 3 double bonds.9. The method of claim 8 , wherein the one or more further 4- to 7-member ring systems comprise heteroatoms.10. The method of claim 1 ...

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Номер записи: 97

06-01-2022 дата публикации

OLIGONUCLEOTIDE-MEDIATED SENSE CODON REASSIGNMENT

Номер: US20220002719A1

Автор: Alexandrov Kirill, CUI Zhenling, MUREEV Sergey

Принадлежит:

Sense codon reassignment to unnatural amino acids (uAAs) represents a powerful approach for introducing novel properties into polypeptides. The main obstacle to this approach is competition between the native isoacceptor tRNA(s) and orthogonal tRNA(s) for the reassigned codon. While several chromatographic and enzymatic procedures for selective deactivation of tRNA isoacceptors in cell-free translation systems exist, they are complex and not scalable. The present invention provides oligonucleotides that hybridise to a tRNA of interest when said tRNA is in a folded state, thereby disrupting the function of the tRNA. The present invention also provides the use of these oligonucleotides in methods for sense codon reassignment and methods for incorporation of uAAs into proteins. The approach described herein represents a new direction in genetic code reassignment with numerous practical applications. 148-. (canceled)49. An oligonucleotide that hybridises to a tRNA of interest when said tRNA is in a folded state , thereby disrupting the function of the tRNA.50. The oligonucleotide of claim 49 , wherein the oligonucleotide hybridises to:(a) the region of the tRNA of interest spanning from the anticodon stem-loop to the variable loop;(b) the region of the tRNA of interest spanning from the anticodon stem-loop to the T stem-loop;(c) the region of the tRNA of interest spanning from the T stem-loop to the 3′CCA-end; or(d) the region of the tRNA of interest spanning from the D stem-loop to the anticodon stem-loop.51. The oligonucleotide of claim 49 , wherein:{'i': E. coli', 'E. coli', 'L. tarentolae, 'sup': Ser', 'Arg', 'Ser, 'sub': GCU', 'CCU', 'GCU, '(a) the oligonucleotide hybridises to a region of the tRNA of interest corresponding to nucleotides N34-47j or N8-47k of tRNA; N31-53 of tRNA; or N56-76 of tRNA; or'}{'sub': 'd', '(b) the oligonucleotide hybridises to the tRNA of interest in a folded state with a Kof between 0.1-100 nM.'}52. The oligonucleotide of claim 49 , ...

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Номер записи: 98

06-01-2022 дата публикации

POLYNUCLEOTIDE AGENTS TARGETING AMINOLEVULINIC ACID SYNTHASE-1 (ALAS1) AND USES THEREOF

Номер: US20220002734A1

Автор: Hinkle Gregory

Принадлежит:

The invention relates to polynucleotide agents, e.g., antisense polynucleotide agents, targeting the ALAS1 gene, and methods of using such agents to alter (e.g., inhibit) expression of ALAS1 and to treat ALAS1 associated diseases, e.g., porphyria. 1. (canceled)2. (canceled)3. A single-stranded antisense polynucleotide agent for inhibiting expression of aminolevulinic acid synthase-1 (ALAS1) , wherein the agent comprises at least 8 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequences listed in Tables 3 and 4 , and wherein at least one of the contiguous nucleotides is a modified nucleotide.4. The agent of claim 3 , wherein substantially all of the nucleotides of the antisense polynucleotide agent are modified nucleotides.5. The agent of claim 3 , which is 10 to 40 nucleotides in length; 10 to 30 nucleotides in length; 18 to 30 nucleotides in length; or 10 to 24 nucleotides in length.6. The agent of claim 3 , wherein the modified nucleotide comprises a modified sugar moiety selected from the group consisting of: a 2′-O-methoxyethyl modified sugar moiety claim 3 , a 2′-methoxy modified sugar moiety claim 3 , a 2′-O-alkyl modified sugar moiety claim 3 , and a bicyclic sugar moiety.7. The agent of claim 3 , wherein the modified nucleotide is a 5-methylcytosine.8. The agent of claim 3 , wherein the modified nucleotide comprises a modified internucleoside linkage.9. The agent of claim 3 , comprising a plurality of 2′-deoxynucleotides flanked on each side by at least one nucleotide having a modified sugar moiety.10. The agent of claim 9 , wherein the agent is a gapmer comprising a gap segment comprised of linked 2′-deoxynucleotides positioned between a 5′ and a 3′ wing segment.11. The agent of claim 3 , comprisinga gap segment consisting of linked deoxynucleotides;a 5′-wing segment consisting of linked nucleotides;a 3′-wing segment consisting of linked nucleotides;wherein the gap segment is positioned between the 5′-wing ...

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Номер записи: 99

02-01-2020 дата публикации

CONJUGATES COMPRISING OCULAR ANGIOGENESIS GROWTH FACTOR APTAMERS AND USES THEREOF IN THE DETECTION AND TREATMENT OF OPHTHALMOLOGICAL ANGIOGENESIS INDICATIONS

Номер: US20200000934A1

Автор: ETERY Sharon, MANDEL Yossi, MARKUS Amos, SHOVAL Asaf, Willner Itamar

Принадлежит:

Provided is an antiangiogenic agent in the form of a vehicle, e.g., a nanoparticle associated (directly or indirectly) with at least one ocular angiogenesis growth factor aptamer, wherein said association labile to interaction between the aptamer and an ocular angiogenesis growth factor. 1. An antiangiogenic agent comprising a vehicle having a plurality of nucleic acids associated therewith , each nucleic acid in said plurality of nucleic acids having a sequence comprising at least 9 nucleic acid bases hybridized to at least 9 nucleic acid bases of a complementary nucleic acid sequence comprised within a sequence of at least one ocular angiogenesis growth factor (OAGF) aptamer , wherein said hybridization dissociates upon binding of at least one ocular angiogenesis growth factor to said at least one aptamer.23.-. (canceled)4. The agent according to claim 1 , wherein the vehicle is in the form of a nanoparticle selected from the group consisting of carbon quantum dots (C-dots) claim 1 , graphene oxide nanoparticles claim 1 , DNA based nanoparticles claim 1 , carbon nitride nanoparticles claim 1 , metal organic framework nanoparticles claim 1 , polymeric nanoparticles claim 1 , polysaccharide nanoparticles and combinations thereof.52. The agent according to claim claim 1 , wherein the vehicle is C-dot.6. The agent according to claim 5 , wherein the C-dot is surface-associated with a plurality of nucleic acids claim 5 , each nucleic acid in said plurality of nucleic acids having a sequence comprising at least 9 nucleic acid bases hybridized to at least 9 nucleic acid bases of a complementary nucleic acid sequence comprised within a sequence of at least one ocular angiogenesis growth factor (OAGF) aptamer.7. The agent according to claim 6 , wherein the C-dot is surface-associated with each of the nucleic acids via a covalent bond or the C-dot is surface associated with each of the nucleic acids via non-covalent interaction or the C-dot is functionalized with amine or ...

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Номер записи: 100