JP6129844B2 - 多量体オリゴヌクレオチド化合物 - Google Patents

多量体オリゴヌクレオチド化合物 Download PDF

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JP6129844B2
JP6129844B2 JP2014530879A JP2014530879A JP6129844B2 JP 6129844 B2 JP6129844 B2 JP 6129844B2 JP 2014530879 A JP2014530879 A JP 2014530879A JP 2014530879 A JP2014530879 A JP 2014530879A JP 6129844 B2 JP6129844 B2 JP 6129844B2
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oligonucleotide
linker
seq
compound
targeting
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JP2014527819A (ja
JP2014527819A5 (https=
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オイゲン ウールマン，
オイゲン ウールマン，
マルクス ヴェバー，
マルクス ヴェバー，
ロメッシュ スブラマニアン，
ロメッシュ スブラマニアン，
トマス ディーノ ロッケル，
トマス ディーノ ロッケル，
アーサー エム． クレイグ，
アーサー エム． クレイグ，
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ラナ セラピューティクス インコーポレイテッド
ラナ セラピューティクス インコーポレイテッド
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/00—Structure or type of the nucleic acid
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  • Gastroenterology & Hepatology (AREA)
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  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Saccharide Compounds (AREA)
JP2014530879A 2011-09-14 2012-09-14 多量体オリゴヌクレオチド化合物 Active JP6129844B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161534561P 2011-09-14 2011-09-14
US61/534,561 2011-09-14
PCT/US2012/055535 WO2013040429A1 (en) 2011-09-14 2012-09-14 Multimeric oligonucleotide compounds

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JP2014527819A JP2014527819A (ja) 2014-10-23
JP2014527819A5 JP2014527819A5 (https=) 2015-11-05
JP6129844B2 true JP6129844B2 (ja) 2017-05-17

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US (5) US9580708B2 (https=)
EP (2) EP3533873A1 (https=)
JP (2) JP6129844B2 (https=)
AU (2) AU2012308320C1 (https=)
CA (1) CA2848753C (https=)
DK (1) DK2756080T3 (https=)
HK (1) HK1200484A1 (https=)
IL (1) IL231535A0 (https=)
WO (1) WO2013040429A1 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12458604B2 (en) 2020-10-14 2025-11-04 The Trustees Of The University Of Pennsylvania Methods of lipid nanoparticle manufacture and compositions derived therefrom

Families Citing this family (79)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101141544B1 (ko) 2009-03-13 2012-05-03 한국과학기술원 에스아이알엔에이 다중 접합체 및 이의 제조방법
EP3260540A1 (en) 2010-11-12 2017-12-27 The General Hospital Corporation Polycomb-associated non-coding rnas
HK1200484A1 (zh) 2011-09-14 2015-08-07 Translate Bio Ma, Inc. 多聚寡核苷酸化合物
EP2792746A4 (en) * 2011-12-12 2015-09-16 Nat Cerebral & Cardiovascular Ct OLIGONUCLEOTIDE AND THERAPEUTIC FOR HYPERLIPIDEMIA WITH THIS AS AN ACTIVE SUBSTANCE
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
WO2013173652A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics, Inc. Compositions and methods for modulating gene expression
CA2873766A1 (en) 2012-05-16 2013-11-21 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
AU2013262709A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating MECP2 expression
JP2015523854A (ja) 2012-05-16 2015-08-20 ラナ セラピューティクス インコーポレイテッド Ｓｍｎ遺伝子ファミリー発現を調節するための組成物及び方法
CA2873769A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics Inc. Compositions and methods for modulating hemoglobin gene family expression
US20220098659A1 (en) * 2012-08-14 2022-03-31 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9428794B2 (en) * 2012-09-13 2016-08-30 Takara Bio Usa, Inc. Methods of depleting a target nucleic acid in a sample and kits for practicing the same
EP2895200B1 (en) * 2012-09-14 2019-11-06 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
US10077443B2 (en) 2012-11-15 2018-09-18 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
CN104250298B (zh) * 2013-06-25 2018-02-06 浙江华谱新创科技有限公司 一种艾塞那肽高效分离纯化方法
JP2016531570A (ja) 2013-08-16 2016-10-13 ラナ セラピューティクス インコーポレイテッド ユークロマチン領域を標的とするオリゴヌクレオチド
CA2921457A1 (en) * 2013-08-16 2015-02-19 Rana Therapeutics, Inc. Heterochromatin forming non-coding rnas
AU2014306416B2 (en) * 2013-08-16 2021-02-25 Translate Bio Ma, Inc. Compositions and methods for modulating RNA
US9994846B2 (en) * 2013-10-25 2018-06-12 Regulus Therapeutics Inc. MicroRNA compounds and methods for modulating miR-21 activity
WO2015113922A1 (en) * 2014-01-30 2015-08-06 Roche Innovation Center Copenhagen A/S Poly oligomer compound with biocleavable conjugates
GB201408623D0 (en) 2014-05-15 2014-07-02 Santaris Pharma As Oligomers and oligomer conjugates
BR112016027236A2 (pt) * 2014-05-23 2017-10-17 Genzyme Corp porções de múltiplos oligonucleotídeos em veículo de peptídeo
AU2015269412B2 (en) 2014-06-04 2020-03-12 Exicure Operating Company Multivalent delivery of immune modulators by liposomal spherical nucleic acids for prophylactic or therapeutic applications
TW201613949A (en) 2014-08-07 2016-04-16 Regulus Therapeutics Inc Targeting microRNAs for metabolic disorders
WO2016028940A1 (en) 2014-08-19 2016-02-25 Northwestern University Protein/oligonucleotide core-shell nanoparticle therapeutics
WO2016049512A1 (en) 2014-09-26 2016-03-31 University Of Massachusetts Rna-modulating agents
KR20170078843A (ko) 2014-11-21 2017-07-07 노오쓰웨스턴 유니버시티 구형 핵산 나노입자 접합체의 서열 특이적 세포 흡수
GB201421379D0 (en) * 2014-12-02 2015-01-14 Isis Innovation Ltd And Medical Res Council Molecule
WO2016130943A1 (en) 2015-02-13 2016-08-18 Rana Therapeutics, Inc. Hybrid oligonucleotides and uses thereof
IL316159A (en) * 2015-06-15 2024-12-01 Mpeg La Llc Defined Oligonucleotide Multimers and Methods for Manufacture Thereof
JP6875684B2 (ja) * 2015-09-16 2021-05-26 日本新薬株式会社 筋萎縮症治療用アンチセンス核酸
EP3353306A4 (en) * 2015-09-25 2019-06-05 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
US10801026B2 (en) 2015-10-15 2020-10-13 City Of Hope Compounds and compositions including phosphorothioated oligodeoxynucleotide, and methods of use thereof
WO2017131124A1 (ja) * 2016-01-26 2017-08-03 日産化学工業株式会社 一本鎖オリゴヌクレオチド
WO2017177169A1 (en) 2016-04-08 2017-10-12 Rana Therapeutics, Inc. Multimeric coding nucleic acid and uses thereof
AU2017292184A1 (en) * 2016-07-08 2019-02-07 Staten Biotechnology B.V. Anti-Apoc3 antibodies and methods of use thereof
WO2018013525A1 (en) 2016-07-11 2018-01-18 Translate Bio Ma, Inc. Nucleic acid conjugates and uses thereof
US10465242B2 (en) * 2016-07-14 2019-11-05 University Of Utah Research Foundation Multi-sequence capture system
CN107630015B (zh) * 2016-07-19 2021-03-09 上海市东方医院 一种稳定的dna-rna双链结构
JP2019532027A (ja) 2016-08-17 2019-11-07 ソルスティス バイオロジクス，リミティッド ポリヌクレオチド構築物
EP4035659A1 (en) 2016-11-29 2022-08-03 PureTech LYT, Inc. Exosomes for delivery of therapeutic agents
AU2018216509B2 (en) * 2017-01-31 2024-02-29 Curigin Co.,Ltd. Nucleic acid simultaneously inhibiting expression of mTOR gene and STAT3 gene
CN110337495B (zh) 2017-02-06 2024-03-29 日产化学株式会社 单链寡核苷酸
EP3576752A4 (en) * 2017-02-06 2020-12-16 Mpeg La, LLC MULTIMERIC OLIGONUCLEOTIDES WITH REDUCED RENAL CLEARANCE
US20200131231A1 (en) 2017-02-17 2020-04-30 Oxford University Innovation Limited Cell penetrating peptides
WO2018209270A1 (en) 2017-05-11 2018-11-15 Northwestern University Adoptive cell therapy using spherical nucleic acids (snas)
WO2019006455A1 (en) 2017-06-30 2019-01-03 Solstice Biologics, Ltd. AUXILIARIES OF CHIRAL PHOSPHORAMIDITIS AND METHODS OF USE THEREOF
EP3447154A1 (en) * 2017-08-23 2019-02-27 Instytut Genetyki Sadowej Jolanta Powierska - Czarny Method for detection of mutations, polymorphisms and specific dna sequences on dna matrices with dna imaging techniques for the use in medical diagnostics and forensic genetics
JP6960641B2 (ja) * 2017-11-09 2021-11-05 国立大学法人 東京大学 ｍＲＮＡの安定化方法
WO2019140102A1 (en) * 2018-01-10 2019-07-18 Translate Bio Ma, Inc. Compositions and methods for facilitating delivery of synthetic nucleic acids to cells
MX2020009765A (es) * 2018-03-20 2021-01-08 Tokyo Inst Tech Oligonucleotido antisentido reducido en toxicidad.
US20240254480A1 (en) * 2018-05-31 2024-08-01 Korea University Research And Business Foundation Modified nucleic acid inhibiting micro rna, and use thereof
WO2020018739A1 (en) * 2018-07-18 2020-01-23 University Of Florida Research Foundation Rna silencing nanozymes
US20220193250A1 (en) 2018-08-02 2022-06-23 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy
GB201812980D0 (en) 2018-08-09 2018-09-26 Univ Oxford Innovation Ltd Cell-penetrating peptides
GB201812972D0 (en) 2018-08-09 2018-09-26 Univ Oxford Innovation Ltd Cell-penetrating peptides
IL282818B1 (en) 2018-11-02 2026-04-01 Biomarin Tech Bv Bispecific antisense oligonucleotides for dystrophin exon skipping
CN113453723A (zh) 2018-12-07 2021-09-28 牛津大学科技创新有限公司 接头
US20220088202A1 (en) * 2019-01-23 2022-03-24 Shanghai Jiaotong University Nucleic Acid-Drug Conjugate, Drug Delivery System, Preparation Method Therefor and Use Thereof
CA3132505A1 (en) * 2019-03-04 2020-09-10 Mpeg La, L.L.C. Multimeric oligonucleotides with enhanced bioactivity
CN114072501A (zh) 2019-05-06 2022-02-18 马萨诸塞大学 抗c9orf72寡核苷酸及相关方法
WO2021026490A1 (en) * 2019-08-08 2021-02-11 Mpeg La, L.L.C. Cns targeting with multimeric oligonucleotides
AU2021263932B2 (en) * 2020-04-30 2025-07-03 Mpeg La, L.L.C. Multimeric oligonucleotides with divided strands
CA3178559A1 (en) * 2020-05-19 2021-11-25 Jonathan Miles Brown Orthogonally linked multimeric oligonucleotides
US20240318174A1 (en) * 2021-02-08 2024-09-26 Ractigen Therapeutics Multi-Valent Oligonucleotide Agent and Methods of Use Thereof
WO2023009396A2 (en) * 2021-07-28 2023-02-02 The Regents Of The University Of California Structure-based design of antisense oligonucleotide drugs
WO2023102188A1 (en) * 2021-12-03 2023-06-08 Quralis Corporation Gapmer antisense oligonucleotides with modified backbone chemistries
US20230406888A1 (en) * 2022-04-27 2023-12-21 Sachi Bioworks Inc. Methods and systems for targeting autoimmune and inflammatory pathways using nanoligomers
IL318625A (en) 2022-07-29 2025-03-01 Regeneron Pharma Compositions and methods for transferrin receptor (TFR)-mediated delivery to brain and muscle
WO2024069235A2 (en) 2022-09-30 2024-04-04 Sixfold Bioscience Ltd. Compositions containing oligonucleotides with theranostic applications
AU2023365657A1 (en) * 2022-10-17 2025-05-15 University Of Massachusetts Conjugates of sirna and antisense oligonucleotides (sirnaso) and methods of use in gene silencing
IL320016A (en) 2022-11-04 2025-06-01 Regeneron Pharma Calcium voltage-gated channel auxiliary subunit gamma 1 (cacng1) binding proteins and cacng1-mediated delivery to skeletal muscle
AU2023379457A1 (en) 2022-11-14 2025-05-15 Regeneron Pharmaceuticals, Inc. Compositions and methods for fibroblast growth factor receptor 3-mediated delivery to astrocytes
EP4654982A1 (en) 2023-01-27 2025-12-03 Regeneron Pharmaceuticals, Inc. Modified rhabdovirus glycoproteins and uses thereof
WO2024228030A2 (en) 2023-05-04 2024-11-07 Argonaute RNA Limited Dual silencing
WO2025111500A1 (en) * 2023-11-22 2025-05-30 Ionis Pharmaceuticals, Inc. Modulation of gene expression
WO2026026812A1 (zh) * 2024-07-29 2026-02-05 成都先衍生物技术有限公司 一种具有双靶点基因抑制作用的核酸缀合物及其应用
WO2026026811A1 (zh) * 2024-07-29 2026-02-05 成都先衍生物技术有限公司 一种具有双靶点基因抑制作用的核酸缀合物及其应用

Family Cites Families (253)

* 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
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
WO1983001451A1 (en) 1981-10-23 1983-04-28 Molecular Biosystems Inc Oligonucleotide therapeutic agent and methods 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
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
DE3329892A1 (de) 1983-08-18 1985-03-07 Köster, Hubert, Prof. Dr., 2000 Hamburg Verfahren zur herstellung von oligonucleotiden
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
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
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
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
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
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
AU598946B2 (en) 1987-06-24 1990-07-05 Howard Florey Institute Of Experimental Physiology And Medicine 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
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
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
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
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
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
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
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
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
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US6753423B1 (en) 1990-01-11 2004-06-22 Isis Pharmaceuticals, Inc. Compositions and methods for enhanced biostability and altered biodistribution of oligonucleotides in mammals
US5914396A (en) 1990-01-11 1999-06-22 Isis Pharmaceuticals, Inc. 2'-O-modified nucleosides and phosphoramidites
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
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
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US6395492B1 (en) 1990-01-11 2002-05-28 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
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
AU7579991A (en) 1990-02-20 1991-09-18 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
ES2116977T3 (es) 1990-05-11 1998-08-01 Microprobe Corp Soportes solidos para ensayos de hibridacion de acidos nucleicos y metodos para inmovilizar oligonucleotidos de modo covalente.
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
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
BR9106702A (pt) 1990-07-27 1993-06-08 Isis Pharmaceuticals Inc Analogo de oligonucleotideos e processos para modular a producao de uma proteina por um organismo e para tratar um organismo
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
ES2083593T3 (es) 1990-08-03 1996-04-16 Sterling Winthrop Inc Compuestos y metodos para inhibir la expresion de genes.
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
CA2092002A1 (en) 1990-09-20 1992-03-21 Mark Matteucci 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
WO1992008728A1 (en) 1990-11-08 1992-05-29 Hybridon, Inc. Incorporation of multiple reporter groups on synthetic oligonucleotides
US5965722A (en) 1991-05-21 1999-10-12 Isis Pharmaceuticals, Inc. Antisense inhibition of ras gene with chimeric and alternating oligonucleotides
US7015315B1 (en) 1991-12-24 2006-03-21 Isis Pharmaceuticals, Inc. Gapped oligonucleotides
WO1994008003A1 (en) 1991-06-14 1994-04-14 Isis Pharmaceuticals, Inc. ANTISENSE OLIGONUCLEOTIDE INHIBITION OF THE ras GENE
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
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
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
US6831166B2 (en) 1992-10-23 2004-12-14 Isis Pharmaceuticals, Inc. Derivatized oligonucleotides having improved uptake and other properties
US8153602B1 (en) 1991-11-19 2012-04-10 Isis Pharmaceuticals, Inc. Composition and methods for the pulmonary delivery of nucleic acids
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
US20060270624A1 (en) 1991-12-24 2006-11-30 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
KR940703846A (ko) 1991-12-24 1994-12-12 비. 린네 파샬 갭(gap)이 형성된 2′ 변성된 올리고뉴클레오티드(gapped 2′ modifed oligonucleotides)
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
NL9300058A (nl) 1992-06-18 1994-01-17 Stichting Rega V Z W 1,5-anhydrohexitol nucleoside analoga en farmaceutisch gebruik daarvan.
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
US6346614B1 (en) 1992-07-23 2002-02-12 Hybridon, Inc. Hybrid oligonucleotide phosphorothioates
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
TW244371B (https=) 1992-07-23 1995-04-01 Tri Clover Inc
CA2140542A1 (en) 1992-07-27 1994-02-03 Abeysingle Padmapriya Oligonucleotide alkylphosphonothioates
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
KR960701077A (ko) 1993-01-25 1996-02-24 다알렌 반스톤 올리고누클레오티드 알킬포스포네이트 및 알킬포스포노티오에이트(oligonucleotide alkylphosphonates and alkylphosphonothioates)
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
CA2159629A1 (en) 1993-03-31 1994-10-13 Sanofi Oligonucleotides with amide linkages replacing phosphodiester linkages
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
EP0733059B1 (en) 1993-12-09 2000-09-13 Thomas Jefferson University Compounds and methods for site-directed mutations in eukaryotic cells
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
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
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5734039A (en) 1994-09-15 1998-03-31 Thomas Jefferson University Antisense oligonucleotides targeting cooperating oncogenes
US6608035B1 (en) 1994-10-25 2003-08-19 Hybridon, Inc. Method of down-regulating gene expression
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
US8217015B2 (en) 2003-04-04 2012-07-10 Arrowhead Madison Inc. Endosomolytic polymers
ATE267207T1 (de) 1996-02-14 2004-06-15 Isis Pharmaceuticals Inc Kohlenhydratmodifizierte luckenhafte oligonukleotide
WO1997030064A1 (en) 1996-02-16 1997-08-21 Stichting Rega Vzw Hexitol containing oligonucleotides and their use in antisense strategies
US6015710A (en) 1996-04-09 2000-01-18 The University Of Texas System Modulation of mammalian telomerase by peptide nucleic acids
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US5912332A (en) 1996-07-26 1999-06-15 Hybridon, Inc. Affinity-based purification of oligonucleotides using soluble multimeric 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
US6383808B1 (en) 2000-09-11 2002-05-07 Isis Pharmaceuticals, Inc. Antisense inhibition of clusterin expression
AU1292899A (en) 1997-11-07 1999-05-31 Isis Pharmaceuticals, Inc. Pyrimidine derivatives for labeled binding partners
AU3751299A (en) 1998-04-20 1999-11-08 Ribozyme Pharmaceuticals, Inc. Nucleic acid molecules with novel chemical compositions capable of modulating gene expression
ATE346918T1 (de) 1998-06-19 2006-12-15 Univ Mcgill Auf beta-arabinose, und dessen analogen, basierte antisense oligonukleotide
EP0979869A1 (en) * 1998-08-07 2000-02-16 Hoechst Marion Roussel Deutschland GmbH Short oligonucleotides for the inhibition of VEGF expression
US6228642B1 (en) 1998-10-05 2001-05-08 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of tumor necrosis factor-(α) (TNF-α) expression
US6210892B1 (en) 1998-10-07 2001-04-03 Isis Pharmaceuticals, Inc. Alteration of cellular behavior by antisense modulation of mRNA processing
US6465628B1 (en) 1999-02-04 2002-10-15 Isis Pharmaceuticals, Inc. Process for the synthesis of oligomeric compounds
CZ296576B6 (cs) 1999-02-12 2006-04-12 Sankyo Company Limited Nukleosidový analog a oligonukleotidový analog a farmaceutický prostredek, sonda a primer s jeho obsahem
KR20000065690A (ko) 1999-04-08 2000-11-15 박종구 반응 특이성 및 안정성을 개선시킨 안티센스 올리고 뉴클레오타이드, 안티센스 ｄｎａ 및 그 제조방법
US20080281041A1 (en) 1999-06-07 2008-11-13 Rozema David B Reversibly Masked Polymers
US8137695B2 (en) 2006-08-18 2012-03-20 Arrowhead Madison Inc. Polyconjugates for in vivo delivery of polynucleotides
US6677445B1 (en) 1999-08-27 2004-01-13 Chiron Corporation Chimeric antisense oligonucleotides and cell transfecting formulations thereof
ES2218225T3 (es) 1999-09-10 2004-11-16 Stichting Rega V.Z.W. Nucleosidos carbociclicos y procedimiento para obtenerlos.
IL148916A0 (en) 1999-10-04 2002-09-12 Exiqon As Design of high affinity rnase h recruiting oligonucleotide
US20020068709A1 (en) 1999-12-23 2002-06-06 Henrik Orum Therapeutic uses of LNA-modified oligonucleotides
ES2261270T3 (es) 1999-12-30 2006-11-16 K.U. LEUVEN RESEARCH & DEVELOPMENT Acidos nucleicos que contienen ciclohexeno.
US6602857B1 (en) 2000-01-18 2003-08-05 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US6287860B1 (en) 2000-01-20 2001-09-11 Isis Pharmaceuticals, Inc. Antisense inhibition of MEKK2 expression
US6727355B2 (en) 2000-08-25 2004-04-27 Jcr Pharmaceuticals Co., Ltd. Pharmaceutical composition for treatment of Duchenne muscular dystrophy
ATE293688T1 (de) 2000-09-06 2005-05-15 Univ Mcgill Chimerische antisense-oligonukleotide aus arabinofuranose-analogen und deoxyribose- nukleotide
EP1416972B1 (en) 2000-11-09 2012-02-08 Cold Spring Harbor Laboratory Chimeric molecules to modulate gene expression
MXPA04004056A (es) 2001-10-29 2004-09-10 Univ Mcgill Oligonucleotidos que contienen enlazador aciclico y usos de los mismos.
US20030219402A1 (en) 2002-02-14 2003-11-27 Rutter William J. Chimeric molecules for cleavage in a treated host
US20080207542A1 (en) * 2002-03-26 2008-08-28 Sirna Therapeutics, Inc. RNA inteference mediated inhibition of hepatitis C virus (HVC) gene expression using short interfering nucleic acid (siNA)
WO2003085110A2 (en) 2002-04-05 2003-10-16 Santaris Pharma A/S Oligomeric compounds for the modulation hif-1alpha expression
US20030228690A1 (en) 2002-06-10 2003-12-11 Isis Pharmaceuticals Inc. Antisense modulation of IL-1 receptor-associated kinase-1 expression
US7507808B2 (en) 2002-12-12 2009-03-24 Isis Pharmaceuticals, Inc. Modulation of endothelial lipase expression
US20050130924A1 (en) 2002-06-26 2005-06-16 Monia Brett P. Antisense inhibition via RNAse H-independent reduction in mRNA
US8604183B2 (en) 2002-11-05 2013-12-10 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
US9045518B2 (en) 2002-11-18 2015-06-02 Santaris Pharma A/S Amino-LNA, thio-LNA and alpha-L-oxy-LN
US20040248840A1 (en) 2003-02-10 2004-12-09 Santaris Pharma A/S Oligomeric compounds for the modulation of ras expression
FR2853663B1 (fr) 2003-04-14 2007-08-31 Aventis Pharma Sa Procede d'obtention de lignees de mastocytes a partir de tissus de porcs et procede de production de molecules de type heparine
US20080124317A1 (en) * 2003-06-25 2008-05-29 Orna Mor Diagnos and Treatment of Fibrosis Related Pathology
US7683036B2 (en) 2003-07-31 2010-03-23 Regulus Therapeutics Inc. Oligomeric compounds and compositions for use in modulation of small non-coding RNAs
US20050053981A1 (en) 2003-09-09 2005-03-10 Swayze Eric E. Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini
GB0324854D0 (en) 2003-10-24 2003-11-26 Expresson Biosystems Ltd App/ena antisense
GEP20094767B (en) 2003-10-30 2009-09-10 Coley Pharm Group Inc C-class oligonucleotide analogs with enhanced immunostimulatory potency
US7431915B2 (en) 2003-10-31 2008-10-07 The Regents Of The University Of California Peptides whose uptake by cells is controllable
RU2377301C2 (ru) 2003-12-23 2009-12-27 Сантарис Фарма А/С ОЛИГОМЕРНОЕ СОЕДИНЕНИЕ, ПОНИЖАЮЩЕЕ ЭКСПРЕССИЮ ЧЕЛОВЕЧЕСКОГО ГЕНА Bcl-2, КОНЪЮГАТ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ПРИМЕНЕНИЕ ОЛИГОМЕРНОГО СОЕДИНЕНИЯ ДЛЯ ЛЕЧЕНИЯ РАКА
EP1713332A4 (en) 2004-01-23 2010-08-18 Avi Biopharma Inc ANTISENSE OLIGOMERS AND METHOD FOR INDUCTION OF IMMUNOTHERAPY AND IMMUNOSUPPRESSION
JP4755113B2 (ja) * 2004-01-30 2011-08-24 クアーク・ファーマスーティカルス、インコーポレイテッド 線維性状態およびその他の疾患の治療のための、オリゴリボヌクレオチドおよびその使用方法
US8314226B2 (en) 2004-03-29 2012-11-20 The General Hospital Corporation Oligonucleotide complex compositions and methods of use as gene alteration tools
JP2008500039A (ja) 2004-05-26 2008-01-10 ロゼッタ ジノミクス リミテッド ウイルスｍｉＲＮＡおよびウイルス関連ｍｉＲＮＡならびにその使用
AU2005252663B2 (en) 2004-06-03 2011-07-07 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
US7879992B2 (en) 2005-01-31 2011-02-01 Isis Pharmaceuticals, Inc. Modification of MyD88 splicing using modified oligonucleotides
AU2006213686A1 (en) 2005-02-09 2006-08-17 Avi Bio Pharma, Inc. Antisense composition and method for treating muscle atrophy
DE102005036654A1 (de) 2005-08-04 2007-02-15 Bayer Materialscience Ag Selbstvernetzende PUR-Dispersionen mit Uretdionstruktur
WO2007056826A1 (en) 2005-11-21 2007-05-24 Johnson & Johnson Research Pty Limited Multitargeting interfering rnas and methods of their use and design
US20090011004A1 (en) 2005-12-30 2009-01-08 Philadelphia Health & Education Corp., D/B/A/ Drexel University Of College Of Medicine Improved carriers for delivery of nucleic acid agents to cells and tissues
JP5342881B2 (ja) 2006-01-27 2013-11-13 アイシス ファーマシューティカルズ， インコーポレーテッド ６−修飾された二環式核酸類似体
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
EP1984499B1 (en) 2006-01-27 2015-05-27 Isis Pharmaceuticals, Inc. Oligomeric compounds and compositions for the use in modulation of micrornas
EP1989307B1 (en) * 2006-02-08 2012-08-08 Quark Pharmaceuticals, Inc. NOVEL TANDEM siRNAS
CA2648132C (en) 2006-04-03 2019-05-28 Santaris Pharma A/S Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
EP2023940B1 (en) 2006-05-05 2011-06-22 Isis Pharmaceuticals, Inc. Compounds and methods for modulating expression of sglt2
WO2008029619A1 (fr) 2006-09-07 2008-03-13 Daiichi Sankyo Company, Limited Oligonucléotide antisens ena ayant une action spécifique de la séquence
ES2603379T3 (es) 2006-10-09 2017-02-27 Roche Innovation Center Copenhagen A/S Compuestos antagonistas de ARN para la modulación de PCSK9
WO2008049085A1 (en) 2006-10-18 2008-04-24 Isis Pharmaceuticals, Inc. Antisense compounds
US20080311040A1 (en) * 2007-03-06 2008-12-18 Flagship Ventures METHODS AND COMPOSITIONS FOR IMPROVED THERAPEUTIC EFFECTS WITH siRNA
WO2008113832A2 (en) 2007-03-22 2008-09-25 Santaris Pharma A/S SHORT RNA ANTAGONIST COMPOUNDS FOR THE MODULATION OF TARGET mRNA
MX2010001785A (es) 2007-08-15 2010-03-10 Idera Pharmaceuticals Inc Moduladores de receptores tipo larga distancia.
EP2623599B1 (en) 2007-10-04 2019-01-02 Roche Innovation Center Copenhagen A/S Micromirs
EP2205746A4 (en) 2007-10-04 2010-12-22 Univ Texas MODULATION OF GENE EXPRESSION WITH AGRNA AND GAPS WITH ANTISENSE TRANSCRIPTS AS A TARGET
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
EP2268811A1 (en) 2008-03-07 2011-01-05 Santaris Pharma A/S Pharmaceutical compositions for treatment of microrna related diseases
US8846639B2 (en) 2008-04-04 2014-09-30 Isis Pharmaceutical, Inc. Oligomeric compounds comprising bicyclic nucleosides and having reduced toxicity
WO2009124341A1 (en) 2008-04-07 2009-10-15 The University Of Queensland Rna molecules and uses thereof
CA2635187A1 (en) 2008-06-05 2009-12-05 The Royal Institution For The Advancement Of Learning/Mcgill University Oligonucleotide duplexes and uses thereof
US20110172292A1 (en) 2008-06-30 2011-07-14 Hansen Jens Bo Rode Antidote oligomers
WO2010040112A2 (en) 2008-10-03 2010-04-08 Curna, Inc. Treatment of apolipoprotein-a1 related diseases by inhibition of natural antisense transcript to apolipoprotein-a1
CN102231979B (zh) 2008-10-16 2014-10-29 玛瑞纳生物技术有限公司 基因沉默治疗剂的脂质体有效递送方法和组合物
US20100249214A1 (en) * 2009-02-11 2010-09-30 Dicerna Pharmaceuticals Multiplex dicer substrate rna interference molecules having joining sequences
CA2750561C (en) 2009-01-26 2017-10-10 Protiva Biotherapeutics, Inc. Compositions and methods for silencing apolipoprotein c-iii expression
EP2395085B1 (en) 2009-02-04 2015-06-10 Sungkyunkwan University Foundation for Corporate Collaboration Small interference rna complex with increased intracellular transmission capacity
WO2010120969A1 (en) 2009-04-15 2010-10-21 Board Of Regents, The University Of Texas System Targeting of the mir-30 family and let-7 family as a treatment for heart disease
US20120258104A1 (en) * 2009-07-22 2012-10-11 Cenix Bioscience Gmbh Delivery System and Conjugates For Compound Delivery Via Naturally Occurring Intracellular Transport Routes
DK2470656T3 (da) * 2009-08-27 2015-06-22 Idera Pharmaceuticals Inc Sammensætning til hæmning af genekspression og anvendelser heraf
US9187746B2 (en) * 2009-09-22 2015-11-17 Alnylam Pharmaceuticals, Inc. Dual targeting siRNA agents
EP2490699A1 (en) 2009-10-20 2012-08-29 Santaris Pharma A/S Oral delivery of therapeutically effective lna oligonucleotides
WO2011078672A1 (en) * 2009-12-24 2011-06-30 Prosensa Technologies B.V. Molecule for treating an inflammatory disorder
US20130079505A1 (en) 2010-03-24 2013-03-28 Mirrx Therapeutics A/S Bivalent antisense oligonucleotides
DK2558578T3 (en) 2010-04-13 2016-01-25 Life Technologies Corp CONFIGURATIONS AND METHODS FOR INHIBITION OF nucleic acid function
CN102946906B (zh) 2010-04-23 2015-07-15 弗·哈夫曼-拉罗切有限公司 生产异源多聚体蛋白质
RS56011B1 (sr) 2010-04-29 2017-09-29 Ionis Pharmaceuticals Inc Modulacija ekspresije transtiretina
EP2582397A4 (en) 2010-06-15 2014-10-29 Isis Pharmaceuticals Inc COMPOUNDS AND METHOD FOR MODULATING INTERACTION BETWEEN PROTEINS AND TARGET NUCLEIC ACIDS
GB201010557D0 (en) 2010-06-23 2010-08-11 Mina Therapeutics Ltd RNA molecules and uses thereof
WO2012012467A2 (en) 2010-07-19 2012-01-26 Isis Pharmaceuticals, Inc. Modulation of nuclear-retained rna
EP3260540A1 (en) 2010-11-12 2017-12-27 The General Hospital Corporation Polycomb-associated non-coding rnas
US10000752B2 (en) 2010-11-18 2018-06-19 Curna, Inc. Antagonat compositions and methods of use
DK2655621T3 (en) 2010-12-20 2018-08-13 Massachusetts Gen Hospital Polycomb-associated non-coding RNAS
US8557787B2 (en) * 2011-05-13 2013-10-15 The Board Of Trustees Of The Leland Stanford Junior University Diagnostic, prognostic and therapeutic uses of long non-coding RNAs for cancer and regenerative medicine
HK1200484A1 (zh) 2011-09-14 2015-08-07 Translate Bio Ma, Inc. 多聚寡核苷酸化合物
US9209196B2 (en) 2011-11-30 2015-12-08 Sharp Kabushiki Kaisha Memory circuit, method of driving the same, nonvolatile storage device using the same, and liquid crystal display device
US9404108B2 (en) 2012-03-04 2016-08-02 Bonac Corporation Micro-RMA inhibitor
EA201492119A1 (ru) 2012-05-16 2015-05-29 Рана Терапьютикс, Инк. Композиции и способы для модулирования экспрессии apoa1 и abca1
AU2013262709A1 (en) 2012-05-16 2015-01-22 Rana Therapeutics, Inc. Compositions and methods for modulating MECP2 expression
WO2013173605A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics, Inc. Compositions and methods for modulating pten expression
CA2873766A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics Inc. Compositions and methods for modulating atp2a2 expression
WO2013173652A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics, Inc. Compositions and methods for modulating gene expression
US9567581B2 (en) 2012-08-07 2017-02-14 The General Hospital Corporation Selective reactivation of genes on the inactive X chromosome
EP2895200B1 (en) 2012-09-14 2019-11-06 Translate Bio MA, Inc. Multimeric oligonucleotide compounds
US10077443B2 (en) 2012-11-15 2018-09-18 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
US9580078B2 (en) * 2014-09-25 2017-02-28 Toyota Motor Engineering & Manufacturing North America, Inc. Systems and methods for preheating hybrid vehicles
JP2017533721A (ja) 2014-11-14 2017-11-16 アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． タンパク質の調節のための化合物及び方法

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12458604B2 (en) 2020-10-14 2025-11-04 The Trustees Of The University Of Pennsylvania Methods of lipid nanoparticle manufacture and compositions derived therefrom
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