JP7842458B2 - Ｓｎｐを標的とする化学修飾オリゴヌクレオチド - Google Patents

Ｓｎｐを標的とする化学修飾オリゴヌクレオチド

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Publication number
JP7842458B2
JP7842458B2 JP2022507791A JP2022507791A JP7842458B2 JP 7842458 B2 JP7842458 B2 JP 7842458B2 JP 2022507791 A JP2022507791 A JP 2022507791A JP 2022507791 A JP2022507791 A JP 2022507791A JP 7842458 B2 JP7842458 B2 JP 7842458B2
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Prior art keywords
nucleotides
nucleotide
nucleotide analogs
snp
rna
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JP2022507791A
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Japanese (ja)
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JP2022547790A (ja
JP2022547790A5 (https=
Inventor
コボロバ，アナスタシア
オルターマン，ジュリア
コンロイ，フェイス
フィスター，イーディス
アロニン，ニール
建 山田
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University of Massachusetts Amherst
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University of Massachusetts Amherst
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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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
    • A61K47/544—Phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/554—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
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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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/312—Phosphonates
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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
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
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    • C12N2310/00—Structure or type of the nucleic acid
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    • C12N2310/322—2'-R Modification
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3515—Lipophilic moiety, e.g. cholesterol
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3521—Methyl
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • C12N2310/3533—Halogen
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    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/53—Methods for regulating/modulating their activity reducing unwanted side-effects

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Botany (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
JP2022507791A 2019-08-09 2020-08-07 Ｓｎｐを標的とする化学修飾オリゴヌクレオチド Active JP7842458B2 (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201962885066P 2019-08-09 2019-08-09
US62/885,066 2019-08-09
US202062976168P 2020-02-13 2020-02-13
US62/976,168 2020-02-13
PCT/US2020/045487 WO2021030213A1 (en) 2019-08-09 2020-08-07 Chemically modified oligonucleotides targeting snps

Publications (3)

Publication Number Publication Date
JP2022547790A JP2022547790A (ja) 2022-11-16
JP2022547790A5 JP2022547790A5 (https=) 2023-06-30
JP7842458B2 true JP7842458B2 (ja) 2026-04-08

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JP2022507791A Active JP7842458B2 (ja) 2019-08-09 2020-08-07 Ｓｎｐを標的とする化学修飾オリゴヌクレオチド

Country Status (11)

Country Link
US (2) US12024706B2 (https=)
EP (1) EP4010476A4 (https=)
JP (1) JP7842458B2 (https=)
KR (1) KR20220047989A (https=)
CN (1) CN114502730A (https=)
AU (1) AU2020329155A1 (https=)
BR (1) BR112022002307A2 (https=)
CA (1) CA3149835A1 (https=)
IL (1) IL290329A (https=)
MX (1) MX2022001710A (https=)
WO (1) WO2021030213A1 (https=)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160319278A1 (en) 2015-04-03 2016-11-03 University Of Massachusetts Fully stabilized asymmetric sirna
WO2017030973A1 (en) 2015-08-14 2017-02-23 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
JP7406793B2 (ja) 2017-06-23 2023-12-28 ユニバーシティー オブ マサチューセッツ ２テイル自己デリバリー型ｓｉＲＮＡおよび関連方法
US11279930B2 (en) 2018-08-23 2022-03-22 University Of Massachusetts O-methyl rich fully stabilized oligonucleotides
KR20220047989A (ko) 2019-08-09 2022-04-19 유니버시티 오브 매사추세츠 Snp를 표적화하는 화학적으로 변형된 올리고뉴클레오타이드
WO2021041247A1 (en) * 2019-08-23 2021-03-04 University Of Massachusetts O-methyl rich fully stabilized oligonucleotides
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
WO2021242883A1 (en) 2020-05-26 2021-12-02 University Of Massachusetts Synthetic oligonucleotides having regions of block and cluster modifications
US20240200063A1 (en) * 2021-03-24 2024-06-20 Atalanta Therapeutics, Inc. Microglial gene silencing using double-stranded sirna
EP4314296A2 (en) 2021-03-29 2024-02-07 Alnylam Pharmaceuticals, Inc. Huntingtin (htt) irna agent compositions and methods of use thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160348103A1 (en) 2014-01-27 2016-12-01 The Board Of Trustees Of The Leland Stanford Junior University Oligonucleotides and Methods for Treatment of Cardiomyopathy Using RNA Interference
WO2017132669A1 (en) 2016-01-31 2017-08-03 University Of Massachusetts Branched oligonucleotides

Family Cites Families (217)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US5240848A (en) 1988-11-21 1993-08-31 Monsanto Company Dna sequences encoding human vascular permeability factor having 189 amino acids
US5328470A (en) 1989-03-31 1994-07-12 The Regents Of The University Of Michigan Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor
US5332671A (en) 1989-05-12 1994-07-26 Genetech, Inc. Production of vascular endothelial cell growth factor and DNA encoding same
US5219739A (en) 1989-07-27 1993-06-15 Scios Nova Inc. DNA sequences encoding bVEGF120 and hVEGF121 and methods for the production of bovine and human vascular endothelial cell growth factors, bVEGF120 and hVEGF121
US5194596A (en) 1989-07-27 1993-03-16 California Biotechnology Inc. Production of vascular endothelial cell growth factor
ES2113371T3 (es) 1989-11-16 1998-05-01 Univ Duke Transformacion de celulas epidermicas de tejidos animales con la ayuda de particulas.
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5672697A (en) 1991-02-08 1997-09-30 Gilead Sciences, Inc. Nucleoside 5'-methylene phosphonates
US5252479A (en) 1991-11-08 1993-10-12 Research Corporation Technologies, Inc. Safe vector for gene therapy
US5587308A (en) 1992-06-02 1996-12-24 The United States Of America As Represented By The Department Of Health & Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
JPH0641183A (ja) 1992-07-23 1994-02-15 Mitsubishi Kasei Corp オリゴヌクレオチド単分子膜
US5985558A (en) 1997-04-14 1999-11-16 Isis Pharmaceuticals Inc. Antisense oligonucleotide compositions and methods for the inibition of c-Jun and c-Fos
US5858988A (en) 1993-02-24 1999-01-12 Wang; Jui H. Poly-substituted-phenyl-oligoribo nucleotides having enhanced stability and membrane permeability and methods of use
US6291438B1 (en) 1993-02-24 2001-09-18 Jui H. Wang Antiviral anticancer poly-substituted phenyl derivatized oligoribonucleotides and methods for their use
WO1994022890A1 (en) 1993-03-31 1994-10-13 Sterling Winthop Inc. Novel 5'-substituted nucleosides and oligomers produced therefrom
TW360548B (en) 1993-04-08 1999-06-11 Powderject Res Ltd Products for therapeutic use
EP0763050B1 (en) 1994-06-01 2000-01-05 Hybridon, Inc. Branched oligonucleotide as pathogen-inhibitory agents
WO1996003500A1 (en) 1994-07-26 1996-02-08 Ltt Institute Co., Ltd. Sustance with antiviral activity
US6383814B1 (en) 1994-12-09 2002-05-07 Genzyme Corporation Cationic amphiphiles for intracellular delivery of therapeutic molecules
WO1996033761A1 (en) 1995-04-28 1996-10-31 Medtronic, Inc. Intraparenchymal infusion catheter system
US6025335A (en) 1995-09-21 2000-02-15 Lipitek International, Inc. L-Nucleoside Dimer Compounds and therapeutic uses
US5684143A (en) 1996-02-21 1997-11-04 Lynx Therapeutics, Inc. Oligo-2'-fluoronucleotide N3'->P5' phosphoramidates
US5735814A (en) 1996-04-30 1998-04-07 Medtronic, Inc. Techniques of treating neurodegenerative disorders by brain infusion
US20080119427A1 (en) 1996-06-06 2008-05-22 Isis Pharmaceuticals, Inc. Double Strand Compositions Comprising Differentially Modified Strands for Use in Gene Modulation
US5898031A (en) 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
US5849902A (en) 1996-09-26 1998-12-15 Oligos Etc. Inc. Three component chimeric antisense oligonucleotides
US6177403B1 (en) 1996-10-21 2001-01-23 The Trustees Of The University Of Pennsylvania Compositions, methods, and apparatus for delivery of a macromolecular assembly to an extravascular tissue of an animal
US6042820A (en) 1996-12-20 2000-03-28 Connaught Laboratories Limited Biodegradable copolymer containing α-hydroxy acid and α-amino acid units
AUPO974597A0 (en) 1997-10-10 1997-11-06 Rhone-Poulenc Agro Methods for obtaining plant varieties
US6472375B1 (en) 1998-04-16 2002-10-29 John Wayne Cancer Institute DNA vaccine and methods for its use
US6242589B1 (en) 1998-07-14 2001-06-05 Isis Pharmaceuticals, Inc. Phosphorothioate oligonucleotides having modified internucleoside linkages
EP1016726A1 (en) 1998-12-30 2000-07-05 Introgene B.V. Gene therapy to promote angiogenesis
EP1240337B1 (en) 1999-12-24 2006-08-23 Genentech, Inc. Methods and compositions for prolonging elimination half-times of bioactive compounds
US8202979B2 (en) 2002-02-20 2012-06-19 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
US8273866B2 (en) 2002-02-20 2012-09-25 Merck Sharp & Dohme Corp. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (SINA)
CA2429814C (en) 2000-12-01 2014-02-18 Thomas Tuschl Rna interference mediating small rna molecules
EP1386004A4 (en) 2001-04-05 2005-02-16 Ribozyme Pharm Inc MODULATION OF GENE EXPRESSION ASSOCIATED WITH INFLAMMATORY PROLIFERATION AND GROWTH OF NEURITIES BY METHODS INVOLVING NUCLEIC ACID
EP2447370B1 (en) 2001-09-28 2018-07-18 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. MicroRNA molecules
WO2003053363A2 (en) 2001-12-19 2003-07-03 Millennium Pharmaceuticals, Inc. Human diacylglycerol acyltransferase 2 (dgat2) family members and uses therefor
US20060009409A1 (en) 2002-02-01 2006-01-12 Woolf Tod M Double-stranded oligonucleotides
US9181551B2 (en) 2002-02-20 2015-11-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US20050096284A1 (en) 2002-02-20 2005-05-05 Sirna Therapeutics, Inc. RNA interference mediated treatment of polyglutamine (polyQ) repeat expansion diseases using short interfering nucleic acid (siNA)
US20100240730A1 (en) 2002-02-20 2010-09-23 Merck Sharp And Dohme Corp. RNA Interference Mediated Inhibition of Gene Expression Using Chemically Modified Short Interfering Nucleic Acid (siNA)
US7858367B2 (en) 2002-04-30 2010-12-28 Duke University Viral vectors and methods for producing and using the same
KR101215701B1 (ko) 2002-07-19 2012-12-26 베스 이스라엘 데코니스 메디칼 센터 자간전증 또는 자간의 진단 및 치료 방법
US20050106731A1 (en) 2002-08-05 2005-05-19 Davidson Beverly L. siRNA-mediated gene silencing with viral vectors
US20040241854A1 (en) 2002-08-05 2004-12-02 Davidson Beverly L. siRNA-mediated gene silencing
US7923547B2 (en) 2002-09-05 2011-04-12 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
AU2003285071A1 (en) 2002-10-30 2004-06-07 Nikolaos Avlonitis Antiprotozoal ring-substituted phospholipids
AU2003291755A1 (en) 2002-11-05 2004-06-07 Isis Pharmaceuticals, Inc. Oligomers comprising modified bases for binding cytosine and uracil or thymine and their use
US7250496B2 (en) 2002-11-14 2007-07-31 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory genes and uses thereof
AU2003295600A1 (en) 2002-11-14 2004-06-15 Dharmacon, Inc. Functional and hyperfunctional sirna
WO2006006948A2 (en) 2002-11-14 2006-01-19 Dharmacon, Inc. METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
US7217807B2 (en) 2002-11-26 2007-05-15 Rosetta Genomics Ltd Bioinformatically detectable group of novel HIV regulatory genes and uses thereof
US6913890B2 (en) 2002-12-18 2005-07-05 Palo Alto Research Center Incorporated Process for preparing albumin protein conjugated oligonucleotide probes
AU2003299864A1 (en) 2002-12-27 2004-07-29 P. Radhakrishnan Sirna compounds and methods for the downregulation of gene expression
US20040198640A1 (en) 2003-04-02 2004-10-07 Dharmacon, Inc. Stabilized polynucleotides for use in RNA interference
ES2702942T3 (es) 2003-04-17 2019-03-06 Alnylam Pharmaceuticals Inc Agentes de ARNi modificados
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
PT1633767T (pt) 2003-06-02 2019-02-27 Univ Massachusetts Métodos e composições para controlar a eficácia do silenciamento de arn
US7750144B2 (en) 2003-06-02 2010-07-06 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of RNA silencing
EP1633890B2 (en) 2003-06-02 2020-11-18 University of Massachusetts METHODS AND COMPOSITIONS FOR ENHANCING THE EFFICACY AND SPECIFICITY OF FNAi
DE10326302A1 (de) 2003-06-11 2004-12-30 Gnothis Holding Sa Bi-Fluorophor-markierte Sonden zum Nachweis von Nukleinsäuren
US8680063B2 (en) * 2003-09-12 2014-03-25 University Of Massachusetts RNA interference for the treatment of gain-of-function disorders
WO2008005562A2 (en) 2006-07-07 2008-01-10 University Of Massachusetts Rna silencing compositions and methods for the treatment of huntington's disease
EP2256201A3 (en) 2003-09-18 2012-07-04 Isis Pharmaceuticals, Inc. Modulation of eIF4E expression
EP1709195B1 (en) 2003-12-19 2014-01-22 Novartis Vaccines and Diagnostics, Inc. Cell transfecting formulations of small interfering rna, related compositions and methods of making and use
US20050176045A1 (en) * 2004-02-06 2005-08-11 Dharmacon, Inc. SNP discriminatory siRNA
WO2005077333A2 (en) 2004-02-10 2005-08-25 University Of Florida Research Foundation, Inc. Gel-based delivery of recombinant adeno-associated virus vectors
ES2423060T3 (es) 2004-03-12 2013-09-17 Alnylam Pharmaceuticals, Inc. Agentes iRNA que tienen como diana al VEGF
KR101147147B1 (ko) 2004-04-01 2012-05-25 머크 샤프 앤드 돔 코포레이션 Ｒｎａ 간섭의 오프 타겟 효과 감소를 위한 변형된폴리뉴클레오타이드
US20060014289A1 (en) 2004-04-20 2006-01-19 Nastech Pharmaceutical Company Inc. Methods and compositions for enhancing delivery of double-stranded RNA or a double-stranded hybrid nucleic acid to regulate gene expression in mammalian cells
WO2005116204A1 (ja) 2004-05-11 2005-12-08 Rnai Co., Ltd. Ｒｎａ干渉を生じさせるポリヌクレオチド、および、これを用いた遺伝子発現抑制方法
EP1789553B1 (en) 2004-06-30 2014-03-26 Alnylam Pharmaceuticals Inc. Oligonucleotides comprising a non-phosphate backbone linkage
US7361468B2 (en) 2004-07-02 2008-04-22 Affymetrix, Inc. Methods for genotyping polymorphisms in humans
JP5136766B2 (ja) 2004-12-15 2013-02-06 ユニバーシティ オブ ノース カロライナ アット チャペル ヒル キメラベクター
EP1937066A4 (en) 2005-08-18 2008-12-24 Alnylam Pharmaceuticals Inc METHOD AND COMPOSITIONS FOR THE TREATMENT OF NERVOUS DISEASES
EP1931780B1 (en) 2005-08-29 2016-01-06 Regulus Therapeutics Inc. Antisense compounds having enhanced anti-microrna activity
JP5111385B2 (ja) 2005-10-28 2013-01-09 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 ハンチンチン遺伝子の発現を抑制するための組成物および方法
CN101346393B (zh) 2005-11-02 2015-07-22 普洛体维生物治疗公司 修饰的siRNA分子及其应用
US7825099B2 (en) 2006-01-20 2010-11-02 Quark Pharmaceuticals, Inc. Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes
US20070259827A1 (en) * 2006-01-25 2007-11-08 University Of Massachusetts Compositions and methods for enhancing discriminatory RNA interference
US9198981B2 (en) 2006-02-01 2015-12-01 The University Of Kentucky Modulation of angiogenesis
EP1989307B1 (en) 2006-02-08 2012-08-08 Quark Pharmaceuticals, Inc. NOVEL TANDEM siRNAS
WO2007094218A1 (ja) 2006-02-16 2007-08-23 Gifu University 修飾オリゴヌクレオチド
WO2007095387A2 (en) 2006-02-17 2007-08-23 Dharmacon, Inc. Compositions and methods for inhibiting gene silencing by rna interference
US20090306178A1 (en) 2006-03-27 2009-12-10 Balkrishen Bhat Conjugated double strand compositions for use in gene modulation
US20080039415A1 (en) 2006-08-11 2008-02-14 Gregory Robert Stewart Retrograde transport of sirna and therapeutic uses to treat neurologic disorders
AU2007299705B2 (en) 2006-09-22 2012-09-06 Dharmacon, Inc. Duplex oligonucleotide complexes and methods for gene silencing by RNA interference
CA2666657A1 (en) 2006-10-18 2008-04-24 Nastech Pharmaceutical Company Inc. Nicked or gapped nucleic acid molecules and uses thereof
US8906874B2 (en) 2006-11-09 2014-12-09 Gradalis, Inc. Bi-functional shRNA targeting Stathmin 1 and uses thereof
US20100015706A1 (en) 2007-03-02 2010-01-21 Mdrna, Inc. Nucleic acid compounds for inhibiting hif1a gene expression and uses thereof
WO2008154482A2 (en) 2007-06-08 2008-12-18 Sirnaomics, Inc. Sirna compositions and methods of use in treatment of ocular diseases
WO2009002944A1 (en) 2007-06-22 2008-12-31 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
CA2695420A1 (en) 2007-08-23 2009-02-26 Novartis Ag Methods for detecting oligonucleotides
EP3889261A1 (en) 2007-08-27 2021-10-06 1Globe Health Institute LLC Compositions of asymmetric interfering rna and uses thereof
TW200927177A (en) 2007-10-24 2009-07-01 Nat Inst Of Advanced Ind Scien Lipid-modified double-stranded RNA having potent RNA interference effect
WO2009073809A2 (en) 2007-12-04 2009-06-11 Alnylam Pharmaceuticals, Inc. Carbohydrate conjugates as delivery agents for oligonucleotides
US9029524B2 (en) 2007-12-10 2015-05-12 California Institute Of Technology Signal activated RNA interference
WO2009099991A2 (en) 2008-01-31 2009-08-13 The Brigham And Women's Hospital, Inc. Treatment of cancer
CA2715289C (en) 2008-02-11 2019-12-24 Rxi Pharmaceuticals Corporation Modified rnai polynucleotides and uses thereof
US9217155B2 (en) 2008-05-28 2015-12-22 University Of Massachusetts Isolation of novel AAV'S and uses thereof
US8815818B2 (en) 2008-07-18 2014-08-26 Rxi Pharmaceuticals Corporation Phagocytic cell delivery of RNAI
US20110251258A1 (en) 2008-07-24 2011-10-13 Rxi Pharmaceuticals Corporation Rnai constructs and uses thereof
EP2321414B1 (en) 2008-07-25 2018-01-10 Alnylam Pharmaceuticals, Inc. Enhancement of sirna silencing activity using universal bases or mismatches in the sense strand
EP2342340A1 (en) 2008-09-22 2011-07-13 Rxi Pharmaceuticals Corporation Rna interference in skin indications
ES2794401T3 (es) 2008-10-15 2020-11-18 Axolabs Gmbh Método de detección de oligonucleótidos
CA2962219C (en) 2008-10-22 2020-08-25 Quark Pharmaceuticals, Inc. Methods for treating eye disorders
EP2447274B1 (en) 2008-10-24 2017-10-04 Ionis Pharmaceuticals, Inc. Oligomeric compounds and methods
WO2010059226A2 (en) 2008-11-19 2010-05-27 Rxi Pharmaceuticals Corporation Inhibition of map4k4 through rnai
WO2010078536A1 (en) 2009-01-05 2010-07-08 Rxi Pharmaceuticals Corporation Inhibition of pcsk9 through rnai
US9023820B2 (en) 2009-01-26 2015-05-05 Protiva Biotherapeutics, Inc. Compositions and methods for silencing apolipoprotein C-III expression
US9745574B2 (en) 2009-02-04 2017-08-29 Rxi Pharmaceuticals Corporation RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
KR101141544B1 (ko) 2009-03-13 2012-05-03 한국과학기술원 에스아이알엔에이 다중 접합체 및 이의 제조방법
JP2012521766A (ja) 2009-03-27 2012-09-20 メルク・シャープ・エンド・ドーム・コーポレイション 低分子干渉核酸（ｓｉＮＡ）を用いた高親和性ＩｇＥ受容体α鎖（ＦＣεＲ１α）遺伝子発現のＲＮＡ干渉媒介性阻害
US8309356B2 (en) 2009-04-01 2012-11-13 Yale University Pseudocomplementary oligonucleotides for targeted gene therapy
WO2010118263A1 (en) * 2009-04-08 2010-10-14 University Of Massachusetts Single-nucleotide polymorphism (snp) targeting therapies for the treatment of huntington's disease
US8734809B2 (en) 2009-05-28 2014-05-27 University Of Massachusetts AAV's and uses thereof
GB0910723D0 (en) 2009-06-22 2009-08-05 Sylentis Sau Novel drugs for inhibition of gene expression
EP2470656B1 (en) 2009-08-27 2015-05-06 Idera Pharmaceuticals, Inc. Composition for inhibiting gene expression and uses thereof
NZ714887A (en) 2009-09-11 2019-07-26 Ionis Pharmaceuticals Inc Modulation of huntingtin expression
US20150025122A1 (en) 2009-10-12 2015-01-22 Larry J. Smith Methods and Compositions for Modulating Gene Expression Using Oligonucleotide Based Drugs Administered in vivo or in vitro
US8877439B2 (en) 2009-12-17 2014-11-04 Sirna Therapeutics, Inc. Method for rapidly evaluating performance of short interfering RNA with novel chemical modifications
US8957040B2 (en) * 2010-02-08 2015-02-17 Isis Pharmaceuticals, Inc. Selective reduction of allelic variants
WO2011109698A1 (en) 2010-03-04 2011-09-09 Rxi Pharmaceuticals Corporation Formulations and methods for targeted delivery to phagocyte cells
EP3560503B1 (en) 2010-03-24 2021-11-17 Phio Pharmaceuticals Corp. Rna interference in dermal and fibrotic indications
RU2615143C2 (ru) 2010-03-24 2017-04-04 Адвирна Самодоставляющие PHKi соединения уменьшенного размера
CN103200945B (zh) 2010-03-24 2016-07-06 雷克西制药公司 眼部症候中的rna干扰
WO2011125943A1 (ja) 2010-04-01 2011-10-13 日本新薬株式会社 修飾オリゴヌクレオチド
EP2601204B1 (en) 2010-04-28 2016-09-07 Ionis Pharmaceuticals, Inc. Modified nucleosides and oligomeric compounds prepared therefrom
WO2012005898A2 (en) 2010-06-15 2012-01-12 Alnylam Pharmaceuticals, Inc. Chinese hamster ovary (cho) cell transcriptome, corresponding sirnas and uses thereof
WO2011158924A1 (ja) 2010-06-18 2011-12-22 独立行政法人国立精神・神経医療研究センター 優性アレル発現抑制剤
WO2012003330A2 (en) 2010-06-30 2012-01-05 Stratos Genomics, Inc Multiplexed identification of nucleic acid sequences
WO2012058210A1 (en) 2010-10-29 2012-05-03 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA)
CA2817256A1 (en) 2010-11-12 2012-05-18 The General Hospital Corporation Polycomb-associated non-coding rnas
CN103562205A (zh) 2010-12-16 2014-02-05 沃泰克斯药物股份有限公司 流感病毒复制的抑制剂
CA2822059A1 (en) 2010-12-16 2012-06-21 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
RU2013132681A (ru) 2010-12-16 2015-01-27 Вертекс Фармасьютикалз Инкорпорейтед Ингибиторы репликации вирусов гриппа
AU2011343664B2 (en) 2010-12-17 2015-10-08 Arrowhead Pharmaceuticals, Inc. Galactose cluster-pharmacokinetic modulator targeting moiety for siRNA
CA2828544A1 (en) 2011-03-03 2012-09-07 Quark Pharmaceuticals, Inc. Oligonucleotide modulators of the toll-like receptor pathway
GB201105137D0 (en) * 2011-03-28 2011-05-11 Isis Innovation Therapeutic molecules for use in the suppression of Parkinson's disease
KR102104125B1 (ko) 2011-04-21 2020-05-29 재단법인 한국파스퇴르연구소 소염 화합물
US20140275211A1 (en) 2011-06-21 2014-09-18 Alnylam Pharmaceuticals, Inc. Assays and methods for determining activity of a therapeutic agent in a subject
US20150299696A1 (en) 2012-05-02 2015-10-22 Sirna Therapeutics, Inc. SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
KR101567576B1 (ko) 2012-05-22 2015-11-10 올릭스 주식회사 세포 내 관통능을 가지고 ｒｎａ 간섭을 유도하는 핵산 분자 및 그 용도
US9480752B2 (en) 2012-07-10 2016-11-01 Baseclick Gmbh Anandamide-modified nucleic acid molecules
US20150247141A1 (en) 2012-09-14 2015-09-03 Rana Therapeutics, Inc. Multimeric oligonucleotide compounds
WO2014047649A1 (en) 2012-09-24 2014-03-27 The Regents Of The University Of California Methods for arranging and packing nucleic acids for unusual resistance to nucleases and targeted delivery for gene therapy
CN104837996A (zh) 2012-11-15 2015-08-12 罗氏创新中心哥本哈根有限公司 抗apob反义缀合物化合物
IL292159B1 (en) 2012-12-05 2026-04-01 Alnylam Pharmaceuticals Inc PCSK9 iRNA compositions and methods of using them
US20140200124A1 (en) 2013-01-15 2014-07-17 Karen Michelle JAMES Physical Therapy Device and Methods for Use Thereof
DK2992098T3 (da) 2013-05-01 2019-06-17 Ionis Pharmaceuticals Inc Sammensætninger og fremgangsmåder til modulering af hbv- og ttr-ekspression
KR102234623B1 (ko) 2013-05-22 2021-04-02 알닐람 파마슈티칼스 인코포레이티드 Ｔｍｐｒｓｓ6 조성물 및 이의 사용 방법
EP3007705A4 (en) 2013-06-12 2017-02-15 Oncoimmunin, Inc. Systemic in vivo delivery of oligonucleotides
AU2014282666A1 (en) 2013-06-16 2016-01-07 National University Corporation Tokyo Medical And Dental University Double-stranded antisense nucleic acid with exon-skipping effect
US9862350B2 (en) 2013-08-12 2018-01-09 Tk Holdings Inc. Dual chambered passenger airbag
GB201315141D0 (en) 2013-08-23 2013-10-09 Logicor R & D Ltd Improvements to electric heating systems and method of use thereof
EP3066219B1 (en) 2013-11-08 2018-12-26 Ionis Pharmaceuticals, Inc. Methods for detecting oligonucleotides
US10513710B2 (en) 2014-04-18 2019-12-24 University Of Massachusetts Exosomal loading using hydrophobically modified oligonucleotides
US20170051286A1 (en) 2014-05-01 2017-02-23 Larry J. Smith METHODS AND MODIFICATIONS THAT PRODUCE ssRNAi COMPOUNDS WITH ENHANCED ACTIVITY, POTENCY AND DURATION OF EFFECT
WO2015171918A2 (en) 2014-05-07 2015-11-12 Louisiana State University And Agricultural And Mechanical College Compositions and uses for treatment thereof
AU2015264038B2 (en) 2014-05-22 2021-02-11 Alnylam Pharmaceuticals, Inc. Angiotensinogen (AGT) iRNA compositions and methods of use thereof
US10588980B2 (en) 2014-06-23 2020-03-17 Novartis Ag Fatty acids and their use in conjugation to biomolecules
IL316808A (en) 2014-08-20 2025-01-01 Alnylam Pharmaceuticals Inc Modified double-stranded RNA materials and their uses
CN106795200B (zh) 2014-10-10 2020-06-19 豪夫迈·罗氏有限公司 Galnac亚磷酰胺、其核酸缀合物及其用途
KR102545316B1 (ko) 2014-11-10 2023-06-22 알닐람 파마슈티칼스 인코포레이티드 Ｂ형 간염 바이러스(ｈｂｖ) ｉｒｎａ 조성물 및 그의 이용 방법
HRP20190992T1 (hr) 2014-12-24 2019-09-20 Uniqure Ip B.V. Suprimiranje gena za huntingtin inducirano s rnai
CR20170406A (es) 2015-02-10 2017-11-14 Genzyme Corp Arni variante
CA2979703A1 (en) 2015-03-17 2016-09-22 Arrowhead Pharmaceuticals, Inc. Compositions and methods for inhibiting gene expression of factor xii
PL3277814T3 (pl) 2015-04-03 2020-11-30 University Of Massachusetts Związki oligonukleotydowe ukierunkowane na mrna huntingtyny
US20160319278A1 (en) * 2015-04-03 2016-11-03 University Of Massachusetts Fully stabilized asymmetric sirna
RS62672B1 (sr) 2015-04-03 2021-12-31 Univ Massachusetts Oligonukleotidna jedinjenja za tretman preeklampsije i drugih angiogenskih poremećaja
WO2016164866A1 (en) 2015-04-10 2016-10-13 Hudsonalpha Institute For Biotechnology METHOD FOR BLOCKING miRNA
IL316159A (en) 2015-06-15 2024-12-01 Mpeg La Llc Defined Oligonucleotide Multimers and Methods for Manufacture Thereof
US20170009304A1 (en) 2015-07-07 2017-01-12 Splicingcodes.Com Method and kit for detecting fusion transcripts
IL320434A (en) 2015-07-22 2025-06-01 Wave Life Sciences Ltd Oligonucleotide preparations and methods
EP3331573A4 (en) 2015-08-06 2019-02-27 City of Hope THERAPEUTIC CELL-INTERNALIZING CONJUGATES
WO2017030973A1 (en) 2015-08-14 2017-02-23 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
IL295755A (en) 2015-10-09 2022-10-01 Wave Life Sciences Ltd Oligonucleotide compositions and methods thereof
JP2019513371A (ja) 2016-04-01 2019-05-30 アビディティー バイオサイエンシーズ エルエルシー 核酸ポリペプチド組成物とその使用
US10036024B2 (en) 2016-06-03 2018-07-31 Purdue Research Foundation siRNA compositions that specifically downregulate expression of a variant of the PNPLA3 gene and methods of use thereof for treating a chronic liver disease or alcoholic liver disease (ALD)
CA3033368A1 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
CN110352244B (zh) 2016-09-01 2023-03-21 ProQR治疗上市公司Ⅱ 化学修饰的编辑rna的单链寡核苷酸
DK3607069T3 (da) 2017-04-05 2022-11-21 Silence Therapeutics Gmbh Produkter og sammensætninger
JP2020522510A (ja) 2017-06-02 2020-07-30 ウェイブ ライフ サイエンシズ リミテッドＷａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｌｔｄ． オリゴヌクレオチド組成物及びその使用方法
JP7406793B2 (ja) 2017-06-23 2023-12-28 ユニバーシティー オブ マサチューセッツ ２テイル自己デリバリー型ｓｉＲＮＡおよび関連方法
WO2019035038A1 (en) 2017-08-18 2019-02-21 The Procter & Gamble Company Cleaning agent
CN111163938B (zh) 2017-10-12 2022-09-09 艾利丹尼森公司 低放气清洁胶黏剂
WO2019075419A1 (en) 2017-10-13 2019-04-18 Dicerna Pharmaceuticals, Inc. METHODS AND COMPOSITIONS FOR INHIBITING LDHA EXPRESSION
EP3550021A1 (en) 2018-04-05 2019-10-09 Silence Therapeutics GmbH Products and compositions for inhibiting expression of a target gene
MX2020011570A (es) 2018-05-07 2020-11-24 Alnylam Pharmaceuticals Inc Administracion extrahepatica.
CN120247995A (zh) 2018-05-30 2025-07-04 诺华股份有限公司 脂质修饰的核酸化合物和方法
WO2020033899A1 (en) 2018-08-10 2020-02-13 University Of Massachusetts Modified oligonucleotides targeting snps
US11279930B2 (en) * 2018-08-23 2022-03-22 University Of Massachusetts O-methyl rich fully stabilized oligonucleotides
CN113614232A (zh) 2019-01-18 2021-11-05 马萨诸塞大学 动态药代动力学修饰锚
CN113811311A (zh) 2019-03-15 2021-12-17 马萨诸塞大学 用于组织特异性apoe调节的寡核苷酸
US11820985B2 (en) 2019-03-26 2023-11-21 University Of Massachusetts Modified oligonucleotides with increased stability
JP2022528487A (ja) 2019-03-29 2022-06-13 ユニバーシティ・オブ・マサチューセッツ Ｃ９ｏｒｆ７２のオリゴヌクレオチドベースの調節
KR20220047989A (ko) 2019-08-09 2022-04-19 유니버시티 오브 매사추세츠 Snp를 표적화하는 화학적으로 변형된 올리고뉴클레오타이드
WO2021041247A1 (en) 2019-08-23 2021-03-04 University Of Massachusetts O-methyl rich fully stabilized oligonucleotides
EP4090744A4 (en) 2020-01-17 2024-04-10 Anastasia Khvorova UNIVERSAL DYNAMIC PHARMACOKINETIC MODIFYING ANCHORS
US20210363523A1 (en) 2020-03-18 2021-11-25 University Of Massachusetts Oligonucleotides for mapt modulation
JP7837560B2 (ja) 2020-03-26 2026-03-31 ユニバーシティー オブ マサチューセッツ 安定性の向上を有する修飾オリゴヌクレオチドの合成
ES3014076T3 (en) 2020-03-26 2025-04-16 Nutrivert Inc Lipophilic enantiomers of desacetylglucosamine muramyl dipeptide with anti-inflammatory and growth promoting activity
WO2021195510A1 (en) 2020-03-27 2021-09-30 University Of Massachusetts Dual-acting sirna based modulation of c9orf72
US20210355491A1 (en) 2020-04-20 2021-11-18 University Of Massachusetts Oligonucleotides for msh3 modulation
WO2021242883A1 (en) 2020-05-26 2021-12-02 University Of Massachusetts Synthetic oligonucleotides having regions of block and cluster modifications
EP4158028A4 (en) 2020-05-28 2024-10-02 University Of Massachusetts OLIGONUCLEOTIDES FOR THE MODULATION OF SARS-COV-2
WO2022031591A2 (en) 2020-08-03 2022-02-10 University Of Massachusetts Oligonucleotides for htt-1a modulation
US20220228141A1 (en) 2020-11-23 2022-07-21 University Of Massachusetts Oligonucleotides for dgat2 modulation
CN117677699A (zh) 2021-06-23 2024-03-08 马萨诸塞大学 用于治疗先兆子痫和其他血管生成病症的优化抗flt1寡核苷酸化合物
EP4430191A2 (en) 2021-11-08 2024-09-18 University Of Massachusetts Oligonucleotides for sod1 modulation
WO2023114989A2 (en) 2021-12-17 2023-06-22 University Of Massachusetts Oligonucleotides for mlh3 modulation
US20230340475A1 (en) 2021-12-17 2023-10-26 University Of Massachusetts Oligonucleotides for mlh1 modulation
WO2023133550A2 (en) 2022-01-10 2023-07-13 University Of Massachusetts Oligonucleotides for mecp2 modulation
WO2023201281A2 (en) 2022-04-14 2023-10-19 University Of Massachusetts Oligonucleotides for atn1 modulation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160348103A1 (en) 2014-01-27 2016-12-01 The Board Of Trustees Of The Leland Stanford Junior University Oligonucleotides and Methods for Treatment of Cardiomyopathy Using RNA Interference
WO2017132669A1 (en) 2016-01-31 2017-08-03 University Of Massachusetts Branched oligonucleotides

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SCIENTIFIC REPORTS，2017年，7:12532，1-16

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