RU2017108757A - Лечение связанных с геном-супрессором опухолей заболеваний посредством ингибирования природного транскрипта в антисмысловой ориентации относительно этого гена - Google Patents

Лечение связанных с геном-супрессором опухолей заболеваний посредством ингибирования природного транскрипта в антисмысловой ориентации относительно этого гена Download PDF

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RU2017108757A
RU2017108757A RU2017108757A RU2017108757A RU2017108757A RU 2017108757 A RU2017108757 A RU 2017108757A RU 2017108757 A RU2017108757 A RU 2017108757A RU 2017108757 A RU2017108757 A RU 2017108757A RU 2017108757 A RU2017108757 A RU 2017108757A
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disease
polynucleotide
tumor suppressor
suppressor gene
seq
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RU2017108757A
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RU2746478C2 (ru
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Джозеф КОЛЛАРД
ШЕРМАН Ольга ХОРЬКОВА
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КьюРНА, Инк.
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Claims (14)

1. Способ повышения экспрессии полинуклеотида гена-супрессора опухолей в клетках или тканях пациента in vivo или in vitro, включающий контактирование указанных клеток или тканей с по меньшей мере одним антисмысловым олигонуклеотидом длиной от 19 до 30 нуклеотидов, который избирательно направлен на природный антисмысловой полинуклеотид полинуклеотида гена-супрессора опухолей, причем указанный по меньшей мере один олигонуклеотид выбран из группы, состоящей из SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 12 или SEQ ID NO: 13, посредством чего осуществляется повышение экспрессии полинуклеотида гена-супрессора опухолей в клетках или тканях пациента in vitro, где полинуклеотид гена-супрессора опухолей кодирует Р53 или Р73.
2. Синтетический, модифицированный олигонуклеотид для повышения экспрессии полинуклеотида гена-супрессора опухолей in vivo, где полинуклеотид гена-супрессора опухолей кодирует Р53 или Р73 и указанный по меньшей мере один олигонуклеотид имеет по меньшей мере 90% комплементарность природному антисмысловому полинуклеотиду, выбранному из группы, состоящей из SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 12 или SEQ ID NO: 13, где указанный олигонуклеотид дополнительно включает по меньшей мере одну модификацию, причем по меньшей мере одну модификацию выбирают из по меньшей мере одной модифицированной молекулы сахара, по меньшей мере одной модифицированной межнуклеотидной связи, по меньшей мере одного модифицированного нуклеотида и их комбинаций.
3. Олигонуклеотид по п. 2, в котором по меньшей мере одна модификация включает межнуклеотидную связь, выбираемую из группы, состоящей из фосфоротиоата, алкилфосфоната, фосфородитиоата, алкилфосфонотиоата, фосфорамидата, карбамата, карбоната, триэфира фосфорной кислоты, ацетамидата, карбоксиметилового эфира и их комбинаций.
4. Олигонуклеотид по п. 2, который включает по меньшей мере одну фосфоротиоатную межнуклеотидную связь.
5. Олигонуклеотид по п. 2, который включает остов из фосфоротиоатных межнуклеотидных связей.
6. Олигонуклеотид по п. 2, который включает по меньшей мере один модифицированный нуклеотид, выбираемый из пептидонуклеиновой кислоты, замкнутой нуклеиновой кислоты (LNA), их аналога, производного и комбинаций.
7. Олигонуклеотид по п. 2, который включает множество модификаций, причем указанные модификации включают межнуклеотидные связи, выбираемые из фосфоротиоата, алкилфосфоната, фосфородитиоата, алкилфосфонотиоата, фосфорамидата, карбамата, карбоната, триэфира фосфорной кислоты, ацетамидата, карбоксиметилового эфира и их комбинации.
8. Олигонуклеотид по п. 2, который включает множество модификаций, причем указанные модификации включают модифицированные нуклеотиды, выбираемые из пептидонуклеиновых кислот, замкнутых нуклеиновых кислот (LNA), их аналогов, производных и комбинаций.
9. Олигонуклеотид по п. 2, который включает по меньшей мере одну модифицированную молекулу сахара, выбираемую из 2'-O-метоксиэтил-модифицированной молекулы сахара, 2'-метокси-модифицированной молекулы сахара, 2'-O-алкил-модифицированной молекулы сахара, молекулы бициклического сахара и их комбинации.
10. Олигонуклеотид по п. 2, который включает множество модификаций, причем указанные модификации включают модифицированные молекулы сахара, выбираемые из 2'-O-метоксиэтил-модифицированной молекулы сахара, 2'-метокси-модифицированной молекулы сахара, 2'-O-алкил-модифицированной молекулы сахара, молекулы бициклического сахара и их комбинации
11. Композиция для повышения экспрессии полинуклеотида гена-супрессора опухолей в клетках или тканях пациента in vivo или in vitro, включающая один или несколько олигонуклеотидов по п.2 и фармацевтически приемлемый эксципиент..
12. Композиция по п. 11, где указанный один или несколько олигонуклеотидов включает одну или несколько модификаций, выбранных из фосфоротиоата, метилфосфоната, пептидонуклеиновой кислоты, молекул замкнутых нуклеиновых кислот (LNA) и их комбинаций.
13. Способ профилактики или лечения заболевания, связанного с по меньшей мере одним полинуклеотидом гена-супрессора опухолей и/или по меньшей мере одним кодируемым им продуктом, где полинуклеотид гена-супрессора опухолей кодирует Р53 или Р73, включающий введение пациенту терапевтически эффективной дозы по меньшей мере одного антисмыслового олигонуклеотида по пункту 2, который связывается с природной антисмысловой последовательностью указанного по меньшей мере одного полинуклеотида гена-супрессора опухолей и повышает экспрессию указанного по меньшей мере одного полинуклеотида гена-супрессора опухолей; посредством чего осуществляется профилпктика или лечение заболевания, связанного с по меньшей мере одним полинуклеотидом гена-супрессора опухолей и/или по меньшей мере одним кодируемым им продуктом.
14. Способ по п. 13, в котором заболевание, связанное с по меньшей мере одним полинуклеотидом гена-супрессора опухолей, выбирают из заболевания, связанного со сниженным или повышенным апоптозом, старения тканей/клеток, рака (в том числе злокачественных опухолей, приведенных в таблице 1), аутоиммунного заболевания, болезни иммунодефицита, включающей СПИД, физиологического старения, нейродегенеративного заболевания или нарушения (болезни Альцгеймера, атаксии-телеангиэктазии, болезни Паркинсона, бокового амиотрофического склероза, болезни Хантингтона и т.д.), гиперпластического заболевания (келоида), ревматоидного артрита, коронарной болезни сердца, ишемической гибели клеток, лимфопролиферативного нарушения, атеросклероза, остеопороза, миелодиспластического синдрома, вызванного токсином заболевания, вирусной инфекции, заживления раны, болезни Каудена (CD), болезни Лермитта-Дуклоса (LDD), синдрома Баннайана-Зонана (BZS, также известного как синдром Баннайана-Райли-Рувалкаба, синдром Рувалкаба-Мири-Смита и синдром Райли-Смита), трансплантации, связанного с апоптозом заболевания или нарушения, болезни обмена веществ или метаболического состояния (диабета), болезней или нарушений почки, инфаркта миокарда/сердечной недостаточности, ишемии, сепсиса, воспалительного заболевания, при котором преобладают конкретные гемопоэтические клетки, пролиферативного заболевания или заболевания или нарушения, в случае которого примером терапии является лечение воспалительного заболевания через увеличение апоптоза.
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Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE524547T1 (de) 2006-08-11 2011-09-15 Prosensa Technologies Bv Einzelsträngige oligonukleotide, welche komplementär zu repetitiven elementen sind, zur behandlung von dns-wiederholungen-instabilitäts- assoziierten erkrankungen
KR20110091796A (ko) 2008-12-04 2011-08-12 오피케이오 큐알엔에이, 엘엘씨 종양 억제 유전자에 대한 천연 안티센스 전사체의 억제에 의해 종양 억제 유전자 관련된 질환의 치료
ES2629630T3 (es) 2008-12-04 2017-08-11 Curna, Inc. Tratamiento de enfermedades relacionadas con eritropoyetina (EPO) mediante inhibición del transcrito antisentido natural a EPO
CN102791862B (zh) * 2009-12-31 2017-04-05 库尔纳公司 通过抑制胰岛素受体底物2(irs2)和转录因子e3(tfe3)的天然反义转录物而治疗irs2相关疾病
ES2663598T3 (es) * 2010-07-14 2018-04-16 Curna, Inc. Tratamiento de enfermedades relacionadas con el homólogo de discos grandes (dlg) mediante la inhibición del transcrito antisentido natural a dlg
US9920317B2 (en) 2010-11-12 2018-03-20 The General Hospital Corporation Polycomb-associated non-coding RNAs
EP2638163B1 (en) 2010-11-12 2017-05-17 The General Hospital Corporation Polycomb-associated non-coding rnas
WO2012071238A2 (en) 2010-11-23 2012-05-31 Opko Curna Llc Treatment of nanog related diseases by inhibition of natural antisense transcript to nanog
US10196637B2 (en) 2011-06-08 2019-02-05 Nitto Denko Corporation Retinoid-lipid drug carrier
TWI658830B (zh) 2011-06-08 2019-05-11 日東電工股份有限公司 Ｈｓｐ47表現調控強化用類視色素脂質體
ITMI20120275A1 (it) * 2012-02-24 2013-08-25 Biogenera Societa A Responsabilita Limitata Oligonucleotidi per la modulazione dell'espressione genica e loro usi
SMT201700339T1 (it) * 2012-04-23 2017-09-07 Biomarin Tech B V Oligonucleotidi di modulazione dell'rna con caratteristiche migliorate per il trattamento dei disturbi neuromuscolari
SG11201407483YA (en) 2012-05-16 2014-12-30 Rana Therapeutics Inc Compositions and methods for modulating smn gene family expression
US20150152410A1 (en) 2012-05-16 2015-06-04 Rana Therapeutics, Inc. Compositions and methods for modulating mecp2 expression
EP3511416A1 (en) 2012-05-16 2019-07-17 Translate Bio MA, Inc. Compositions and methods for modulating gene expression
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
AU2013262699A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating ATP2A2 expression
BR112014028634A2 (pt) 2012-05-16 2017-06-27 Rana Therapeutics Inc composições e métodos para modulação da expressão de utrn
AU2013262700A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating hemoglobin gene family expression
CA2873776A1 (en) * 2012-05-16 2013-11-21 Rana Therapeutics Inc. Compositions and methods for modulating pten expression
CA2921457A1 (en) * 2013-08-16 2015-02-19 Rana Therapeutics, Inc. Heterochromatin forming non-coding rnas
US20160230172A1 (en) * 2013-10-14 2016-08-11 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
US10858650B2 (en) 2014-10-30 2020-12-08 The General Hospital Corporation Methods for modulating ATRX-dependent gene repression
US10793855B2 (en) 2015-01-06 2020-10-06 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of C9ORF72 antisense transcript
WO2016149455A2 (en) 2015-03-17 2016-09-22 The General Hospital Corporation The rna interactome of polycomb repressive complex 1 (prc1)
WO2016167780A1 (en) 2015-04-16 2016-10-20 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
EP3316894A4 (en) 2015-07-02 2019-06-19 City of Hope COMPOUNDS AND COMPOSITIONS USING PHOSPHOROIDED OLIGODESOXYNUCLEOTIDE AND METHOD OF USE THEREOF
WO2018085198A1 (en) 2016-11-01 2018-05-11 The Research Foundation For The State University Of New York 5-halouracil-modified micrornas and their use in the treatment of cancer
CN109022462B (zh) 2017-06-08 2021-12-21 中山大学附属第一医院 一种PTEN基因的上游开放阅读框31aa-uORF核苷酸及其编码的多肽的应用
US11648260B2 (en) 2018-03-29 2023-05-16 Technion Research And Development Foundation Limitted Vesicles comprising a PTEN inhibitor and uses of same
CN110184271A (zh) * 2019-06-04 2019-08-30 遵义医科大学珠海校区 一种mRNA-like ncRNA、抑制其表达的反义RNA及两者的应用
RU2763992C1 (ru) * 2020-10-08 2022-01-12 федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр онкологии" Министерства здравоохранения Российской Федерации Способ бесконтактной стимуляции транскрипционной активности гена ингибитора циклинзависимой киназы 2 в опухолевых клетках предстательной железы

Family Cites Families (399)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4534899A (en) 1981-07-20 1985-08-13 Lipid Specialties, Inc. Synthetic phospholipid compounds
US4426330A (en) 1981-07-20 1984-01-17 Lipid Specialties, Inc. Synthetic phospholipid compounds
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
NZ207394A (en) 1983-03-08 1987-03-06 Commw Serum Lab Commission Detecting or determining sequence of amino acids
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
US4754065A (en) 1984-12-18 1988-06-28 Cetus Corporation Precursor to nucleic acid probe
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US4800159A (en) 1986-02-07 1989-01-24 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
DE3788914T2 (de) 1986-09-08 1994-08-25 Ajinomoto Kk Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere.
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
WO1988010264A1 (en) 1987-06-24 1988-12-29 Howard Florey Institute Of Experimental Physiology Nucleoside derivatives
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
ATE151467T1 (de) 1987-11-30 1997-04-15 Univ Iowa Res Found Durch modifikationen an der 3'-terminalen phosphodiesterbindung stabilisierte dna moleküle, ihre verwendung als nukleinsäuresonden sowie als therapeutische mittel zur hemmung der expression spezifischer zielgene
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
US5288512A (en) 1987-12-15 1994-02-22 The Procter & Gamble Company Reduced calorie fats made from triglycerides containing medium and long chain fatty acids
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
WO1989009221A1 (en) 1988-03-25 1989-10-05 University Of Virginia Alumni Patents Foundation Oligonucleotide n-alkylphosphoramidates
NL8800756A (nl) 1988-03-25 1989-10-16 Vereniging Voor Christelijk Wetenschappelijk Onderwijs Genetisch gemanipuleerde plantecellen en planten, alsmede daarvoor bruikbaar recombinant dna.
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5354844A (en) 1989-03-16 1994-10-11 Boehringer Ingelheim International Gmbh Protein-polycation conjugates
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5227170A (en) 1989-06-22 1993-07-13 Vestar, Inc. Encapsulation process
US6203976B1 (en) 1989-07-18 2001-03-20 Osi Pharmaceuticals, Inc. Methods of preparing compositions comprising chemicals capable of transcriptional modulation
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5356633A (en) 1989-10-20 1994-10-18 Liposome Technology, Inc. Method of treatment of inflamed tissues
US5527528A (en) 1989-10-20 1996-06-18 Sequus Pharmaceuticals, Inc. Solid-tumor treatment method
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
EP0497875B1 (en) 1989-10-24 2000-03-22 Isis Pharmaceuticals, Inc. 2' modified oligonucleotides
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5457189A (en) 1989-12-04 1995-10-10 Isis Pharmaceuticals Antisense oligonucleotide inhibition of papillomavirus
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5580575A (en) 1989-12-22 1996-12-03 Imarx Pharmaceutical Corp. Therapeutic drug delivery systems
US5469854A (en) 1989-12-22 1995-11-28 Imarx Pharmaceutical Corp. Methods of preparing gas-filled liposomes
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US5852188A (en) 1990-01-11 1998-12-22 Isis Pharmaceuticals, Inc. Oligonucleotides having chiral phosphorus linkages
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
WO1991013080A1 (en) 1990-02-20 1991-09-05 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
US6034233A (en) 1990-05-04 2000-03-07 Isis Pharmaceuticals Inc. 2'-O-alkylated oligoribonucleotides and phosphorothioate analogs complementary to portions of the HIV genome
EP0745689A3 (en) 1990-05-11 1996-12-11 Microprobe Corporation A dipstick for a nucleic acid hybridization assay
IE66205B1 (en) 1990-06-14 1995-12-13 Paul A Bartlett Polypeptide analogs
US5650489A (en) 1990-07-02 1997-07-22 The Arizona Board Of Regents Random bio-oligomer library, a method of synthesis thereof, and a method of use thereof
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
DE69126530T2 (de) 1990-07-27 1998-02-05 Isis Pharmaceutical, Inc., Carlsbad, Calif. Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
JPH06502300A (ja) 1990-08-03 1994-03-17 サノフィ 遺伝子発現の抑制のための化合物及び方法
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
EP0549686A4 (en) 1990-09-20 1995-01-18 Gilead Sciences Inc Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
CA2095212A1 (en) 1990-11-08 1992-05-09 Sudhir Agrawal Incorporation of multiple reporter groups on synthetic oligonucleotides
WO1992008796A1 (en) 1990-11-13 1992-05-29 Immunex Corporation Bifunctional selectable fusion genes
JP3220180B2 (ja) 1991-05-23 2001-10-22 三菱化学株式会社 薬剤含有タンパク質結合リポソーム
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US6307040B1 (en) 1992-03-05 2001-10-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
US5474796A (en) 1991-09-04 1995-12-12 Protogene Laboratories, Inc. Method and apparatus for conducting an array of chemical reactions on a support surface
NZ244306A (en) 1991-09-30 1995-07-26 Boehringer Ingelheim Int Composition for introducing nucleic acid complexes into eucaryotic cells, complex containing nucleic acid and endosomolytic agent, peptide with endosomolytic domain and nucleic acid binding domain and preparation
US5521291A (en) 1991-09-30 1996-05-28 Boehringer Ingelheim International, Gmbh Conjugates for introducing nucleic acid into higher eucaryotic cells
US5576302A (en) 1991-10-15 1996-11-19 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity
US5661134A (en) 1991-10-15 1997-08-26 Isis Pharmaceuticals, Inc. Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity
ES2103918T3 (es) 1991-10-17 1997-10-01 Ciba Geigy Ag Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios.
US6335434B1 (en) 1998-06-16 2002-01-01 Isis Pharmaceuticals, Inc., Nucleosidic and non-nucleosidic folate conjugates
US5605662A (en) 1993-11-01 1997-02-25 Nanogen, Inc. Active programmable electronic devices for molecular biological analysis and diagnostics
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
US5573905A (en) 1992-03-30 1996-11-12 The Scripps Research Institute Encoded combinatorial chemical libraries
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
IL101600A (en) 1992-04-15 2000-02-29 Yissum Res Dev Co Synthetic partially phosphorothioated antisense oligodeoxynucleotides and pharmaceutical compositions containing them
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
US5288514A (en) 1992-09-14 1994-02-22 The Regents Of The University Of California Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support
US6710174B2 (en) 2001-09-13 2004-03-23 Isis Pharmaceuticals, Inc. Antisense inhibition of vascular endothelial growth factor receptor-1 expression
CA2125871A1 (en) 1992-10-15 1994-04-28 Keishi Miwa Process for preparing major histocompatibility antigen class ii protein and materials in which the same is bound
US5583020A (en) 1992-11-24 1996-12-10 Ribozyme Pharmaceuticals, Inc. Permeability enhancers for negatively charged polynucleotides
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
JP3351476B2 (ja) 1993-01-22 2002-11-25 三菱化学株式会社 リン脂質誘導体及びそれを含有するリポソーム
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
US5395619A (en) 1993-03-03 1995-03-07 Liposome Technology, Inc. Lipid-polymer conjugates and liposomes
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
EP0691968B1 (en) 1993-03-30 1997-07-16 Sanofi Acyclic nucleoside analogs and oligonucleotide sequences containing them
EP0691977B1 (en) 1993-03-31 1997-11-26 Sanofi Oligonucleotides with amide linkages replacing phosphodiester linkages
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
US5462854A (en) 1993-04-19 1995-10-31 Beckman Instruments, Inc. Inverse linkage oligonucleotides for chemical and enzymatic processes
EP0698092B1 (en) 1993-05-11 2007-07-25 The University Of North Carolina At Chapel Hill Antisense oligonucleotides which combat aberrant splicing and methods of using the same
EP0804590A1 (en) 1993-05-21 1997-11-05 Targeted Genetics Corporation Bifunctional selectable fusion genes based on the cytosine deaminase (cd) gene
US5534259A (en) 1993-07-08 1996-07-09 Liposome Technology, Inc. Polymer compound and coated particle composition
CZ287157B6 (en) * 1993-07-13 2000-10-11 Rhone Poulenc Rorer Sa Defective recombinant adenovirus and pharmaceutical preparation in which said adenovirus is comprised
US5417978A (en) 1993-07-29 1995-05-23 Board Of Regents, The University Of Texas System Liposomal antisense methyl phosphonate oligonucleotides and methods for their preparation and use
JP3484197B2 (ja) 1993-09-03 2004-01-06 アイシス・ファーマシューティカルス・インコーポレーテッド アミン誘導化ヌクレオシドおよびオリゴヌクレオシド
US5491084A (en) 1993-09-10 1996-02-13 The Trustees Of Columbia University In The City Of New York Uses of green-fluorescent protein
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
EP1352956A1 (en) 1993-11-30 2003-10-15 McGILL UNIVERSITY Inhibition of DNA methyltransferase
US5908779A (en) 1993-12-01 1999-06-01 University Of Connecticut Targeted RNA degradation using nuclear antisense RNA
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
KR100386337B1 (ko) 1993-12-09 2004-03-24 토마스 제퍼슨 대학교 진핵세포에서부위-특이적돌연변이를위한화합물과그방법
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5595756A (en) 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5593853A (en) 1994-02-09 1997-01-14 Martek Corporation Generation and screening of synthetic drug libraries
WO1995022618A1 (en) 1994-02-22 1995-08-24 Dana-Farber Cancer Institute Nucleic acid delivery system, method of synthesis and uses thereof
US5902880A (en) 1994-08-19 1999-05-11 Ribozyme Pharmaceuticals, Inc. RNA polymerase III-based expression of therapeutic RNAs
US5539083A (en) 1994-02-23 1996-07-23 Isis Pharmaceuticals, Inc. Peptide nucleic acid combinatorial libraries and improved methods of synthesis
US6551618B2 (en) 1994-03-15 2003-04-22 University Of Birmingham Compositions and methods for delivery of agents for neuronal regeneration and survival
US6015880A (en) 1994-03-16 2000-01-18 California Institute Of Technology Method and substrate for performing multiple sequential reactions on a matrix
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5807522A (en) 1994-06-17 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods for fabricating microarrays of biological samples
US5543152A (en) 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US5525735A (en) 1994-06-22 1996-06-11 Affymax Technologies Nv Methods for synthesizing diverse collections of pyrrolidine compounds
US5549974A (en) 1994-06-23 1996-08-27 Affymax Technologies Nv Methods for the solid phase synthesis of thiazolidinones, metathiazanones, and derivatives thereof
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5591721A (en) 1994-10-25 1997-01-07 Hybridon, Inc. Method of down-regulating gene expression
US6645943B1 (en) 1994-10-25 2003-11-11 Hybridon, Inc. Method of down-regulating gene expression
US5512295A (en) 1994-11-10 1996-04-30 The Board Of Trustees Of The Leland Stanford Junior University Synthetic liposomes for enhanced uptake and delivery
GB9501465D0 (en) 1995-01-25 1995-03-15 King S College London Nucleoside phosphorothioate derivatives,synthesis and use thereof
DE19502912A1 (de) 1995-01-31 1996-08-01 Hoechst Ag G-Cap Stabilisierte Oligonucleotide
IT1275862B1 (it) 1995-03-03 1997-10-24 Consiglio Nazionale Ricerche Trascritto antisenso associato ad alcuni tipi di cellule tumorali ed oligodeossinucleotidi sintetici utili nella diagnosi e nel trattamento
IT1276642B1 (it) 1995-03-03 1997-11-03 Consiglio Nazionale Ricerche Trascritto antisenso presente in linfociti b ed oligodeossinucleotidi sintetici utili per inibirne l'azione
US5543165A (en) 1995-06-06 1996-08-06 Hill; Julie B. Process of making a soluble tea product with champagne-like properties
US5739311A (en) 1995-06-07 1998-04-14 Gen-Probe Incorporated Enzymatic synthesis of phosphorothioate oligonucleotides using restriction endonucleases
AU6113396A (en) 1995-06-14 1997-01-15 Regents Of The University Of California, The Novel high affinity human antibodies to tumor antigens
US5569588A (en) 1995-08-09 1996-10-29 The Regents Of The University Of California Methods for drug screening
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
CN1308450C (zh) * 1995-11-30 2007-04-04 德克萨斯州立大学董事会 诊断和治疗肿瘤的方法及组合物
CA2749312A1 (en) 1996-02-14 1997-08-21 Novartis Ag Sugar-modified gapped oligonucleotides
EP0888385B1 (en) 1996-03-14 2003-08-20 Genentech, Inc. Gdnf receptor and uses thereof
JP2000509259A (ja) 1996-04-17 2000-07-25 ヘキスト・マリオン・ルセル・ドイチユラント・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング 血管内皮増殖因子（ＶＥｇＦ／ＶＰＦ）発現のアンチセンス阻害剤
US5786213A (en) 1996-04-18 1998-07-28 Board Of Regents, The University Of Texas System Inhibition of endogenous gastrin expression for treatment of colorectal cancer
US5756710A (en) 1996-06-05 1998-05-26 The Trustees Of Columbia University In City Of New York Phosphorothioate oligonucleotides that bind to the V3-loop and uses thereof
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US20040161777A1 (en) * 1996-06-06 2004-08-19 Baker Brenda F. Modified oligonucleotides for use in RNA interference
US20070275921A1 (en) * 1996-06-06 2007-11-29 Isis Pharmaceuticals, Inc. Oligomeric Compounds That Facilitate Risc Loading
US5849902A (en) 1996-09-26 1998-12-15 Oligos Etc. Inc. Three component chimeric antisense oligonucleotides
US5739119A (en) 1996-11-15 1998-04-14 Galli; Rachel L. Antisense oligonucleotides specific for the muscarinic type 2 acetylcholine receptor MRNA
US7008776B1 (en) 1996-12-06 2006-03-07 Aventis Pharmaceuticals Inc. Compositions and methods for effecting the levels of high density lipoprotein (HDL) cholesterol and apolipoprotein AI very low density lipoprotein (VLDL) cholesterol and low density lipoprotein (LDL) cholesterol
US7235653B2 (en) 1996-12-31 2007-06-26 Isis Pharmaceuticals, Inc. Oligonucleotide compositions and methods for the modulation of the expression of B7 protein
US6127533A (en) * 1997-02-14 2000-10-03 Isis Pharmaceuticals, Inc. 2'-O-aminooxy-modified oligonucleotides
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
DE19710159A1 (de) * 1997-03-12 1998-10-01 Hoechst Ag In vitro Transkriptionsverfahren zum Screening von Naturstoffen und anderen chemischen Substanzen
US6013786A (en) 1997-08-22 2000-01-11 Hybridon, Inc. MDM2-specific antisense oligonucleotides
EP2253639A1 (en) 1997-09-12 2010-11-24 Exiqon A/S Bi- and tri-cyclic nucleoside, nucleotide and oligonucleoide analogues
US7572582B2 (en) 1997-09-12 2009-08-11 Exiqon A/S Oligonucleotide analogues
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US7285288B1 (en) 1997-10-03 2007-10-23 Board Of Regents, The University Of Texas System Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides
US7294459B1 (en) 1997-10-15 2007-11-13 President And Fellows Of Harvard College Cell regulatory genes, encoded products, and uses related thereto
US6034883A (en) 1998-01-29 2000-03-07 Tinney; Charles E. Solid state director for beams
US6175409B1 (en) 1999-04-02 2001-01-16 Symyx Technologies, Inc. Flow-injection analysis and variable-flow light-scattering methods and apparatus for characterizing polymers
US20040186071A1 (en) 1998-04-13 2004-09-23 Bennett C. Frank Antisense modulation of CD40 expression
US20030228597A1 (en) * 1998-04-13 2003-12-11 Cowsert Lex M. Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation
US7321828B2 (en) 1998-04-13 2008-01-22 Isis Pharmaceuticals, Inc. System of components for preparing oligonucleotides
US6221587B1 (en) 1998-05-12 2001-04-24 Isis Pharmceuticals, Inc. Identification of molecular interaction sites in RNA for novel drug discovery
UA61997C2 (en) 1998-05-26 2003-12-15 Icn Pharmaceuticals Nucleosides with bicyclic sugar constituent, oligonucleotide and antiviral pharmaceutical composition
US6833361B2 (en) 1998-05-26 2004-12-21 Ribapharm, Inc. Nucleosides having bicyclic sugar moiety
WO1999066946A1 (en) * 1998-06-24 1999-12-29 Trustees Of The University Of Pennsylvania Compositions and methods for inducing apoptosis in e6-expressing cells
US6100090A (en) 1999-06-25 2000-08-08 Isis Pharmaceuticals Inc. Antisense inhibition of PI3K p85 expression
US20030139359A1 (en) 2001-12-04 2003-07-24 Isis Pharmaceuticals Inc. Antisense modulation of phospholipid scramblase 3 expression
US6867294B1 (en) 1998-07-14 2005-03-15 Isis Pharmaceuticals, Inc. Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages
US6242589B1 (en) 1998-07-14 2001-06-05 Isis Pharmaceuticals, Inc. Phosphorothioate oligonucleotides having modified internucleoside linkages
US6214986B1 (en) 1998-10-07 2001-04-10 Isis Pharmaceuticals, Inc. Antisense modulation of bcl-x expression
WO2000027424A2 (en) 1998-11-06 2000-05-18 Alcon Laboratories, Inc. Upregulation of endogenous prostaglandins to lower intraocular pressure
US5985663A (en) 1998-11-25 1999-11-16 Isis Pharmaceuticals Inc. Antisense inhibition of interleukin-15 expression
JP4994533B2 (ja) 1999-01-27 2012-08-08 デイビツド・エル・ベツカー コネキシンに対するアンチセンスヌクレオチドを含む配合物
AU758956B2 (en) 1999-02-12 2003-04-03 Daiichi Sankyo Company, Limited Novel nucleosides and oligonucleotide analogues
DE60037938T2 (de) 1999-02-26 2009-01-29 The University Of British Columbia, Vancouver Antisense-therapie für trpm-2
US20040137423A1 (en) 1999-03-15 2004-07-15 Hayden Michael R. Compositions and methods for modulating HDL cholesterol and triglyceride levels
WO2000055318A2 (en) 1999-03-15 2000-09-21 University Of British Columbia Abc1 polypeptide and methods and reagents for modulating cholesterol levels
IL145417A0 (en) 1999-03-18 2002-06-30 Exiqon As Detection of mutations in genes by specific lna primers
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
DE60029314T2 (de) 1999-03-24 2007-07-12 Exiqon A/S Verbesserte Synthese für -2.2.1. I Bicyclo-Nukleoside
US6734291B2 (en) 1999-03-24 2004-05-11 Exiqon A/S Synthesis of [2.2.1]bicyclo nucleosides
WO2000057837A2 (en) 1999-03-26 2000-10-05 Aventis Pharmaceuticals Products Inc. Compositions and methods for effecting the levels of cholesterol
WO2000061770A2 (en) 1999-04-08 2000-10-19 Chiron Corporation Enhancement of the immune response for vaccine and gene therapy applications
WO2000063365A1 (en) 1999-04-21 2000-10-26 Pangene Corporation Locked nucleic acid hybrids and methods of use
AU776362B2 (en) 1999-05-04 2004-09-09 Roche Innovation Center Copenhagen A/S L-ribo-LNA analogues
US20030233670A1 (en) 2001-12-04 2003-12-18 Edgerton Michael D. Gene sequences and uses thereof in plants
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
DE19925073C2 (de) 1999-06-01 2001-07-19 Stefan Weiss Nucleinsäuremoleküle mit spezifischer Erkennung von nativem PrP·S··c·, Herstellung und Verwendung
US6656730B1 (en) 1999-06-15 2003-12-02 Isis Pharmaceuticals, Inc. Oligonucleotides conjugated to protein-binding drugs
CA2383871A1 (en) 1999-06-25 2001-01-04 Genset S.A. A novel bap28 gene and protein
US20040006031A1 (en) 2002-07-02 2004-01-08 Isis Pharmaceuticals Inc. Antisense modulation of HMG-CoA reductase expression
US6147200A (en) 1999-08-19 2000-11-14 Isis Pharmaceuticals, Inc. 2'-O-acetamido modified monomers and oligomers
WO2001021631A2 (en) 1999-09-20 2001-03-29 Millennium Pharmaceuticals, Inc. Secreted proteins and uses thereof
BR0014236A (pt) * 1999-09-25 2002-10-15 Univ Iowa Res Found cidos nucléicos imunoestimuladores
US6617442B1 (en) 1999-09-30 2003-09-09 Isis Pharmaceuticals, Inc. Human Rnase H1 and oligonucleotide compositions thereof
IL148922A0 (en) 1999-10-06 2002-09-12 Quark Biotech Inc Method for enrichment of natural antisense messenger rna
US6986988B2 (en) 1999-10-06 2006-01-17 Quark Biotech, Inc. Method for enrichment of natural antisense messenger RNA
JP4377494B2 (ja) * 1999-10-22 2009-12-02 東芝テック株式会社 情報入力装置
WO2001051630A1 (en) 2000-01-07 2001-07-19 Baylor University Antisense compositions and methods
DE60122285D1 (de) 2000-01-14 2006-09-28 Us Gov Health & Human Serv Methonocarbacycloalkylanaloga von nucleosiden
US6303374B1 (en) 2000-01-18 2001-10-16 Isis Pharmaceuticals Inc. Antisense modulation of caspase 3 expression
US6287860B1 (en) 2000-01-20 2001-09-11 Isis Pharmaceuticals, Inc. Antisense inhibition of MEKK2 expression
JP2001247459A (ja) 2000-03-03 2001-09-11 Oakland Uniservices Ltd 癌の組み合わせ療法
US6936467B2 (en) 2000-03-27 2005-08-30 University Of Delaware Targeted chromosomal genomic alterations with modified single stranded oligonucleotides
IL151948A0 (en) 2000-03-27 2003-04-10 Univ Delaware Oligonucleotides for targeted alteration of a genetic sequence and methods utilizing the same
US7402434B2 (en) 2000-05-08 2008-07-22 Newman Stuart A Splice choice antagonists as therapeutic agents
EP1294754A1 (en) 2000-06-29 2003-03-26 Pharma Pacific Pty. Ltd. Interferon-alpha induced gene
JP2004505047A (ja) 2000-07-28 2004-02-19 キャンサー・リサーチ・テクノロジー・リミテッド 複合治療による癌治療
WO2002018388A1 (fr) 2000-08-29 2002-03-07 Takeshi Imanishi Analogues de nucleosides et derives d'oligonucleotides renfermant ces analogues
ATE385505T1 (de) 2000-09-02 2008-02-15 Gruenenthal Gmbh Antisense oligonukleotide gegen vr 1
US6444464B1 (en) 2000-09-08 2002-09-03 Isis Pharmaceuticals, Inc. Antisense modulation of E2F transcription factor 2 expression
WO2002024717A1 (en) 2000-09-20 2002-03-28 Isis Pharmaceuticals, Inc. Antisense modulation of flip-c expression
AU2002210295A1 (en) 2000-10-13 2002-04-22 Institut De Cardiologie De Montreal Antisense oligonucleotide directed toward mammalian vegf receptor genes and uses thereof
US20030228618A1 (en) 2000-11-24 2003-12-11 Erez Levanon Methods and systems for identifying naturally occurring antisense transcripts and methods, kits and arrays utilizing same
US20050222029A1 (en) 2001-01-04 2005-10-06 Myriad Genetics, Incorporated Compositions and methods for treating diseases
US7423142B2 (en) 2001-01-09 2008-09-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of anti-apoptotic genes
US20020147165A1 (en) 2001-02-22 2002-10-10 Isis Pharmaceuticals, Inc. Antisense modulation of calreticulin expression
JP2004531238A (ja) 2001-02-26 2004-10-14 ファーマ パシフィック プロプライエタリー リミテッド インターフェロン−アルファ誘導遺伝子
WO2002085309A2 (en) * 2001-04-24 2002-10-31 Epigenesis Pharmaceuticals, Inc. Composition, formulations & kits for treatment of respiratory & lung disease with anti-sense oligonucleotides & a bronchodilating agent
AUPR497101A0 (en) 2001-05-14 2001-06-07 Queensland University Of Technology Polynucleotides and polypeptides linked to cancer and/or tumorigenesi
IL143379A (en) 2001-05-24 2013-11-28 Yissum Res Dev Co Oligonucleotide against human ache isoform r and its uses
US7053195B1 (en) 2001-06-12 2006-05-30 Syngenta Participatious Ag Locked nucleic acid containing heteropolymers and related methods
US7153954B2 (en) 2001-07-12 2006-12-26 Santaris Pharma A/S Method for preparation of LNA phosphoramidites
CA2453183C (en) 2001-07-12 2016-05-10 University Of Massachusetts In vivo production of small interfering rnas that mediate gene silencing
US7425545B2 (en) 2001-07-25 2008-09-16 Isis Pharmaceuticals, Inc. Modulation of C-reactive protein expression
US20030096772A1 (en) 2001-07-30 2003-05-22 Crooke Rosanne M. Antisense modulation of acyl CoA cholesterol acyltransferase-2 expression
US7259150B2 (en) 2001-08-07 2007-08-21 Isis Pharmaceuticals, Inc. Modulation of apolipoprotein (a) expression
US7060809B2 (en) 2001-09-04 2006-06-13 Exiqon A/S LNA compositions and uses thereof
AU2002327945A1 (en) 2001-09-17 2003-04-01 Eirx Therapeutics Limited Human delta-n p73 molecules and uses thereof
WO2003025177A2 (fr) * 2001-09-17 2003-03-27 Molecular Engines Laboratories Sequences impliquees dans les phenomenes de suppression tumorale, reversion tumorale, apoptose et/ou resistance aux virus et leur utilisation comme medicaments
US20040214766A1 (en) 2001-10-01 2004-10-28 Kari Alitalo VEGF-C or VEGF-D materials and methods for treatment of neuropathologies
CA2457821A1 (en) 2001-10-10 2003-04-24 Societe Des Produits Nestle S.A. Coffee plant with reduced .alpha.-d-galactosidase activity
US7125982B1 (en) 2001-12-05 2006-10-24 Frayne Consultants Microbial production of nuclease resistant DNA, RNA, and oligo mixtures
US6965025B2 (en) 2001-12-10 2005-11-15 Isis Pharmaceuticals, Inc. Antisense modulation of connective tissue growth factor expression
CA2365811A1 (en) 2001-12-21 2003-06-21 Institut De Cardiologie A new gene therapy using antisense strategy to estrogen receptors (er .alpha. and/or er .beta.) to optimize vascular healing and cardioprotection after vascular injury
GB0130955D0 (en) 2001-12-24 2002-02-13 Cancer Res Ventures Expression system
KR20030056538A (ko) 2001-12-28 2003-07-04 주식회사 웰진 리본형 안티센스 올리고뉴클레오티드에 의한 형질전이성장 인자-β1의 효과적 저해제 개발
US20030191075A1 (en) 2002-02-22 2003-10-09 Cook Phillip Dan Method of using modified oligonucleotides for hepatic delivery
US20050143357A1 (en) 2002-02-25 2005-06-30 Ake Pousette Vitamin d upregulated protein 1 (vdup-) methods and uses thereof
US7144995B2 (en) 2002-03-08 2006-12-05 Glen Research Corporation Fluorescent nitrogenous base and nucleosides incorporating same
GB2386836B (en) 2002-03-22 2006-07-26 Cancer Res Ventures Ltd Anti-cancer combinations
US7169916B2 (en) 2002-04-01 2007-01-30 Isis Pharmaceuticals, Inc. Chloral-free DCA in oligonucleotide synthesis
US20050215504A1 (en) 2002-04-02 2005-09-29 Bennett C F Antisense modulation of sterol regulatory element-binding protein-1 expression
CA2480311C (en) 2002-04-05 2015-01-27 Santaris Pharma A/S Oligomeric compounds for the modulation of hif-1alpha expression
US7569575B2 (en) 2002-05-08 2009-08-04 Santaris Pharma A/S Synthesis of locked nucleic acid derivatives
US6808906B2 (en) 2002-05-08 2004-10-26 Rigel Pharmaceuticals, Inc. Directionally cloned random cDNA expression vector libraries, compositions and methods of use
US7199107B2 (en) 2002-05-23 2007-04-03 Isis Pharmaceuticals, Inc. Antisense modulation of kinesin-like 1 expression
US7148342B2 (en) 2002-07-24 2006-12-12 The Trustees Of The University Of Pennyslvania Compositions and methods for sirna inhibition of angiogenesis
US20040033480A1 (en) 2002-08-15 2004-02-19 Wong Norman C.W. Use of resveratrol to regulate expression of apolipoprotein A1
AU2003270537B2 (en) 2002-09-10 2008-03-20 The Samuel Roberts Noble Foundation, Inc. Methods and compositions for production of flavonoid and isoflavonoid nutraceuticals
AU2003283966A1 (en) 2002-09-25 2004-04-23 Pharmacia Corporation Antisense modulation of farnesoid x receptor expression
EP2272958A1 (en) 2002-09-26 2011-01-12 ISIS Pharmaceuticals, Inc. Modulation of forkhead box O1A expression
GB2394658A (en) 2002-11-01 2004-05-05 Cancer Rec Tech Ltd Oral anti-cancer composition
WO2004041838A1 (en) 2002-11-01 2004-05-21 University Of Massachusetts Regulation of transcription elongation factors
EP1562970A4 (en) 2002-11-01 2006-04-12 Univ Pennsylvania COMPOSITIONS AND METHODS FOR INHIBITING HIF-1 ALPHA WITH ARNS
AU2003295387A1 (en) * 2002-11-05 2004-06-03 Isis Parmaceuticals, Inc. Modified oligonucleotides for use in rna interference
AU2003291721A1 (en) * 2002-11-05 2004-06-03 Isis Pharmaceuticals, Inc. Phosphorous-linked oligomeric compounds and their use in gene modulation
EP1562971B1 (en) 2002-11-05 2014-02-12 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
US20060009410A1 (en) 2002-11-13 2006-01-12 Crooke Rosanne M Effects of apolipoprotein B inhibition on gene expression profiles in animals
EP2305813A3 (en) * 2002-11-14 2012-03-28 Dharmacon, Inc. Fuctional and hyperfunctional sirna
ATE442152T1 (de) 2002-11-18 2009-09-15 Santaris Pharma As Antisense-entwurf
US7314750B2 (en) * 2002-11-20 2008-01-01 Affymetrix, Inc. Addressable oligonucleotide array of the rat genome
US7144999B2 (en) 2002-11-23 2006-12-05 Isis Pharmaceuticals, Inc. Modulation of hypoxia-inducible factor 1 alpha expression
US7713738B2 (en) 2003-02-10 2010-05-11 Enzon Pharmaceuticals, Inc. Oligomeric compounds for the modulation of survivin expression
US7598227B2 (en) 2003-04-16 2009-10-06 Isis Pharmaceuticals Inc. Modulation of apolipoprotein C-III expression
US7339051B2 (en) 2003-04-28 2008-03-04 Isis Pharmaceuticals, Inc. Compositions and methods for the treatment of severe acute respiratory syndrome (SARS)
EP1628993A4 (en) * 2003-05-16 2010-04-07 Rosetta Inpharmatics Llc METHOD AND COMPOSITIONS FOR RNA INTERFERENCE
EP1660512A4 (en) 2003-06-02 2009-12-23 Isis Pharmaceuticals Inc Oligonucleotide Synthesis with Alternative Solvents
JP4579911B2 (ja) 2003-06-03 2010-11-10 アイシス・ファーマシューティカルズ・インコーポレイテッド スルビビン発現の調節
US7825235B2 (en) 2003-08-18 2010-11-02 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
EP2256200A3 (en) 2003-09-18 2012-07-18 Isis Pharmaceuticals, Inc. Modulation of eIF4E expression
US20070009899A1 (en) * 2003-10-02 2007-01-11 Mounts William M Nucleic acid arrays for detecting gene expression in animal models of inflammatory diseases
WO2005038013A1 (en) 2003-10-07 2005-04-28 Isis Pharmaceuticals, Inc. Artisense oligonucleotides optimized for kidney targeting
WO2005045034A2 (en) 2003-10-23 2005-05-19 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED TREATMENT OF PARKINSON DISEASE USING SHORT INTERERING NUCLEIC ACID (siNA)
AU2004303464B2 (en) 2003-12-23 2009-10-01 Santaris Pharma A/S Oligomeric compounds for the modulation of BCL-2
CA2553199C (en) 2004-01-12 2014-03-25 The Trustees Of The University Of Pennsylvania System for up-regulating bone morphogenetic protein (bmp) gene expression in bone cells via the application of fields generated by specific electric and electromagnetic signals
US7468431B2 (en) 2004-01-22 2008-12-23 Isis Pharmaceuticals, Inc. Modulation of eIF4E-BP2 expression
GB0403041D0 (en) 2004-02-11 2004-03-17 Milner Anne J Induction of apoptosis
US20050221354A1 (en) * 2004-02-18 2005-10-06 Wyeth Nucleic acid arrays for monitoring expression profiles of drug target genes
EP1566202A1 (en) 2004-02-23 2005-08-24 Sahltech I Göteborg AB Use of resistin antagonists in the treatment of rheumatoid arthritis
US7402574B2 (en) 2004-03-12 2008-07-22 Avi Biopharma, Inc. Antisense composition and method for treating cancer
US8394947B2 (en) * 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
US7297786B2 (en) 2004-07-09 2007-11-20 University Of Iowa Research Foundation RNA interference in respiratory epitheial cells
US7427675B2 (en) 2004-08-23 2008-09-23 Isis Pharmaceuticals, Inc. Compounds and methods for the characterization of oligonucleotides
EP1805197A1 (en) * 2004-09-27 2007-07-11 Med Biogene Inc Hematological cancer profiling system
ES2353638T3 (es) * 2004-11-09 2011-03-03 Santaris Pharma A/S Oligonucleótidos de lna y el tratamiento del cáncer.
US7589190B2 (en) 2004-11-09 2009-09-15 Enzon Pharmaceuticals, Inc. Potent LNA oligonucleotides for the inhibition of HIF-1A expression
US7220549B2 (en) 2004-12-30 2007-05-22 Helicos Biosciences Corporation Stabilizing a nucleic acid for nucleic acid sequencing
CA2608964A1 (en) 2005-06-27 2007-01-04 Alnylam Pharmaceuticals, Inc. Rnai modulation of hif-1 and therapeutic uses thereof
US20070213292A1 (en) * 2005-08-10 2007-09-13 The Rockefeller University Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
WO2007028065A2 (en) 2005-08-30 2007-03-08 Isis Pharmaceuticals, Inc. Chimeric oligomeric compounds for modulation of splicing
CN101365801B (zh) 2005-10-28 2013-03-27 阿尔尼拉姆医药品有限公司 抑制亨廷顿基因表达的组合物和方法
JP4929288B2 (ja) 2005-11-04 2012-05-09 アルナイラム ファーマシューティカルズ， インコーポレイテッド Ｎａｖ１．８遺伝子の発現を抑制するための組成物および方法
EP2641970B1 (en) * 2005-11-17 2014-12-24 Board of Regents, The University of Texas System Modulation of gene expression by oligomers targeted to chromosomal DNA
CA2631713A1 (en) 2005-12-02 2007-09-13 Sirtris Pharmaceuticals, Inc. Modulators of cdc2-like kinases (clks) and methods of use thereof
CN101374964B (zh) 2005-12-09 2013-07-17 贝勒研究院 外周血液白细胞转录模式的模块水平分析
US20070213274A1 (en) 2005-12-20 2007-09-13 Oy Jurilab Ltd Novel genes and markers associated with high-density lipoprotein-cholesterol (HDL-C)
CN100356377C (zh) 2005-12-20 2007-12-19 无锡永中科技有限公司 文档显示方法
JP5713377B2 (ja) * 2005-12-28 2015-05-07 ザ スクリプス リサーチ インスティテュート 薬物標的としての天然アンチセンスおよび非コードｒｎａ転写物
EP2314594B1 (en) 2006-01-27 2014-07-23 Isis Pharmaceuticals, Inc. 6-modified bicyclic nucleic acid analogs
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
KR20170061189A (ko) 2006-03-31 2017-06-02 알닐람 파마슈티칼스 인코포레이티드 Ｅｇ5 유전자의 발현을 억제하는 이본쇄 리보핵산
AU2007257093A1 (en) 2006-05-05 2007-12-13 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of PCSK9
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
WO2007134181A2 (en) 2006-05-11 2007-11-22 Isis Pharmaceuticals, Inc. 5'-modified bicyclic nucleic acid analogs
CA2915441A1 (en) 2006-05-11 2007-11-22 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the pcsk9 gene
EP1867338A1 (en) 2006-05-30 2007-12-19 Université Libre De Bruxelles Pharmaceutical composition comprising apolipoproteins for the treatment of human diseases
US20080199961A1 (en) * 2006-08-25 2008-08-21 Avi Biopharma, Inc. ANTISENSE COMPOSITION AND METHOD FOR INHIBITION OF miRNA BIOGENESIS
WO2008057556A2 (en) 2006-11-06 2008-05-15 Beth Israel Deaconess Medical Center Identification and use of small molecules to modulate ese-1 transcription factor function and to treat ese-1 transcription factor associated diseases
WO2008066672A2 (en) 2006-11-06 2008-06-05 Beth Israel Deaconess Medical Center Identification and use of small molecules to modulate transcription factor function and to treat transcription factor associated diseases
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US20100169996A1 (en) 2007-01-19 2010-07-01 Lionel Navarro Methods and compositions for modulating the sirna and rna-directed-dna methylation pathways
US20100255117A1 (en) 2007-04-06 2010-10-07 The Johns Hopkins University Methods and compositions for the treatment of cancer
US20080293142A1 (en) 2007-04-19 2008-11-27 The Board Of Regents For Oklahoma State University Multiple shRNA Expression Vectors and Methods of Construction
ES2563485T3 (es) 2008-07-01 2016-03-15 Monsanto Technology Llc Construcciones de ADN recombinante y procedimientos para modular la expresión de un gen diana
RU2604489C2 (ru) 2008-10-03 2016-12-10 КьюРНА,Инк.,US Лечение заболеваний, связанных с аполипопротеином-а1, путем ингибирования природного антисмыслового транскрипта аполипопротеина-а1
EP2177615A1 (en) 2008-10-10 2010-04-21 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method for a genome wide identification of expression regulatory sequences and use of genes and molecules derived thereof for the diagnosis and therapy of metabolic and/or tumorous diseases
US8606289B2 (en) 2008-11-10 2013-12-10 Qualcomm Incorporated Power headroom-sensitive scheduling
WO2010058227A2 (en) 2008-11-22 2010-05-27 The University Of Bristol NOVEL USES OF VEGFxxxB
KR20110091796A (ko) 2008-12-04 2011-08-12 오피케이오 큐알엔에이, 엘엘씨 종양 억제 유전자에 대한 천연 안티센스 전사체의 억제에 의해 종양 억제 유전자 관련된 질환의 치료
WO2013080784A1 (ja) 2011-11-30 2013-06-06 シャープ株式会社 メモリ回路とその駆動方法、及び、これを用いた不揮発性記憶装置、並びに、液晶表示装置

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