TW202315943A - 用於治療子癇前症及其它血管新生病症的最佳化抗flt1寡核苷酸化合物 - Google Patents

用於治療子癇前症及其它血管新生病症的最佳化抗flt1寡核苷酸化合物 Download PDF

Info

Publication number
TW202315943A
TW202315943A TW111123258A TW111123258A TW202315943A TW 202315943 A TW202315943 A TW 202315943A TW 111123258 A TW111123258 A TW 111123258A TW 111123258 A TW111123258 A TW 111123258A TW 202315943 A TW202315943 A TW 202315943A
Authority
TW
Taiwan
Prior art keywords
nucleotides
strand
dsrna
antisense strand
righteous
Prior art date
Application number
TW111123258A
Other languages
English (en)
Chinese (zh)
Inventor
安娜塔西亞 赫沃羅瓦
維奈許 哈里哈藍
莎拉 戴維斯
阿南斯 卡魯曼希
Original Assignee
麻薩諸塞大學
美商貝斯以色列女執事醫療中心公司
維奈許 哈里哈藍
阿南斯 卡魯曼希
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 麻薩諸塞大學, 美商貝斯以色列女執事醫療中心公司, 維奈許 哈里哈藍, 阿南斯 卡魯曼希 filed Critical 麻薩諸塞大學
Publication of TW202315943A publication Critical patent/TW202315943A/zh

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C12N15/1138—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 against receptors or cell surface proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/312—Phosphonates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Saccharide Compounds (AREA)
TW111123258A 2021-06-23 2022-06-22 用於治療子癇前症及其它血管新生病症的最佳化抗flt1寡核苷酸化合物 TW202315943A (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202163214224P 2021-06-23 2021-06-23
US63/214,224 2021-06-23

Publications (1)

Publication Number Publication Date
TW202315943A true TW202315943A (zh) 2023-04-16

Family

ID=84544941

Family Applications (1)

Application Number Title Priority Date Filing Date
TW111123258A TW202315943A (zh) 2021-06-23 2022-06-22 用於治療子癇前症及其它血管新生病症的最佳化抗flt1寡核苷酸化合物

Country Status (13)

Country Link
US (2) US11702659B2 (https=)
EP (1) EP4359539A4 (https=)
JP (2) JP7758907B2 (https=)
KR (1) KR20240040729A (https=)
CN (1) CN117677699A (https=)
AR (1) AR126207A1 (https=)
AU (1) AU2022299169A1 (https=)
BR (1) BR112023026862A2 (https=)
CA (1) CA3174095A1 (https=)
IL (1) IL309334A (https=)
MX (1) MX2023015523A (https=)
TW (1) TW202315943A (https=)
WO (1) WO2022271786A1 (https=)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3277811B1 (en) 2015-04-03 2020-12-23 University of Massachusetts Fully stabilized asymmetric sirna
US10633653B2 (en) * 2015-08-14 2020-04-28 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
WO2017132669A1 (en) 2016-01-31 2017-08-03 University Of Massachusetts Branched oligonucleotides
CA3033368A1 (en) * 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
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
JP7627042B2 (ja) 2018-08-23 2025-02-05 ユニバーシティー オブ マサチューセッツ Ｏ－メチルリッチ完全安定化オリゴヌクレオチド
CN113614232A (zh) 2019-01-18 2021-11-05 马萨诸塞大学 动态药代动力学修饰锚
MX2022001710A (es) 2019-08-09 2022-05-10 Univ Massachusetts Oligonucleótidos modificados químicamente dirigidos a los snp.
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
AU2024296743A1 (en) 2023-07-13 2026-02-26 Comanche Biopharma Corp. Formulations of nucleic acid compounds and uses thereof

Family Cites Families (163)

* 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
US5194596A (en) 1989-07-27 1993-03-16 California Biotechnology Inc. Production of vascular endothelial cell growth factor
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
ATE162219T1 (de) 1989-11-16 1998-01-15 Univ Duke Transformation von tierischen hautzellen mit hilfe von partikeln
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
US6291438B1 (en) 1993-02-24 2001-09-18 Jui H. Wang Antiviral anticancer poly-substituted phenyl derivatized oligoribonucleotides and methods for their use
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
TW404844B (en) 1993-04-08 2000-09-11 Oxford Biosciences Ltd Needleless syringe
KR970703357A (ko) 1994-06-01 1997-07-03 다알렌 반스톤 병원체-저해제로서의, 측쇄를 가지는 올리고누클레오티드(branched oligonu-cleotides as pathogen-inhibitory agents)
US6383814B1 (en) 1994-12-09 2002-05-07 Genzyme Corporation Cationic amphiphiles for intracellular delivery of therapeutic molecules
AU5545596A (en) 1995-04-28 1996-11-18 Medtronic, Inc. Intraparenchymal infusion catheter system
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
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
US6472375B1 (en) 1998-04-16 2002-10-29 John Wayne Cancer Institute DNA vaccine and methods for its use
EP1016726A1 (en) 1998-12-30 2000-07-05 Introgene B.V. Gene therapy to promote angiogenesis
EP2180054A1 (en) 1999-12-24 2010-04-28 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)
WO2002081628A2 (en) 2001-04-05 2002-10-17 Ribozyme Pharmaceuticals, Incorporated Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies
US20040259247A1 (en) 2000-12-01 2004-12-23 Thomas Tuschl Rna interference mediating small rna molecules
EP2390331B1 (en) 2001-09-28 2018-04-25 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. MicroRNA molecules
US20060009409A1 (en) 2002-02-01 2006-01-12 Woolf Tod M Double-stranded oligonucleotides
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)
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)
AU2003223775A1 (en) 2002-04-30 2003-11-17 Duke University Adeno-associated viral vectors and methods for their production from hybrid adenovirus and for their use
ES2534926T3 (es) 2002-07-19 2015-04-30 Beth Israel Deaconess Medical Center Métodos para tratar la preeclampsia
US20040241854A1 (en) 2002-08-05 2004-12-02 Davidson Beverly L. siRNA-mediated gene silencing
US7956176B2 (en) 2002-09-05 2011-06-07 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US8604183B2 (en) 2002-11-05 2013-12-10 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
EP2305812A3 (en) 2002-11-14 2012-06-06 Dharmacon, Inc. Fuctional and hyperfunctional sirna
US7250496B2 (en) 2002-11-14 2007-07-31 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory genes and uses thereof
US7790867B2 (en) 2002-12-05 2010-09-07 Rosetta Genomics Inc. Vaccinia virus-related nucleic acids and microRNA
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
US7851615B2 (en) 2003-04-17 2010-12-14 Alnylam Pharmaceuticals, Inc. Lipophilic conjugated iRNA agents
DK1620544T3 (en) 2003-04-17 2019-01-14 Alnylam Pharmaceuticals Inc MODIFIED iRNA AGENTS
US7750144B2 (en) 2003-06-02 2010-07-06 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of RNA silencing
DK1633767T3 (en) 2003-06-02 2019-03-25 Univ Massachusetts METHODS AND COMPOSITIONS FOR MANAGING THE EFFECT OF RNA SILENCING
ES2357116T5 (es) 2003-06-02 2021-09-03 Univ Massachusetts Métodos y composiciones para mejorar la eficacia y especificad de FNAi
US8680063B2 (en) 2003-09-12 2014-03-25 University Of Massachusetts RNA interference for the treatment of gain-of-function disorders
KR100750788B1 (ko) 2003-09-18 2007-08-20 아이시스 파마수티컬즈 인코포레이티드 ｅＩＦ4Ｅ 발현의 조정
CA2549720C (en) 2003-12-19 2013-10-15 Chiron Corporation Cell transfecting formulations of small interfering rna, related compositions and methods of making and use
WO2005077333A2 (en) 2004-02-10 2005-08-25 University Of Florida Research Foundation, Inc. Gel-based delivery of recombinant adeno-associated virus vectors
AU2005222902B2 (en) 2004-03-12 2010-06-10 Alnylam Pharmaceuticals, Inc. iRNA agents targeting 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
EP1752536A4 (en) 2004-05-11 2008-04-16 Alphagen Co Ltd POLYNUCLEOTIDE CAUSING RNA INTERFERENCE AND METHOD OF REGULATING GENE EXPRESSION WITH THE USE OF THE SAME
AU2005252663B2 (en) 2004-06-03 2011-07-07 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
EP1828390B1 (en) 2004-12-15 2012-06-13 The University Of North Carolina At Chapel Hill Chimeric vectors
EP2239328A3 (en) 2005-08-18 2011-01-05 Alnylam Pharmaceuticals Inc. Methods and compositions for treating neurological disease
WO2007027894A2 (en) 2005-08-29 2007-03-08 Isis Pharmaceuticals, Inc. Antisense compounds having enhanced anti-microrna activity
WO2007051045A2 (en) 2005-10-28 2007-05-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of huntingtin gene
US8101741B2 (en) 2005-11-02 2012-01-24 Protiva Biotherapeutics, Inc. Modified siRNA molecules and uses thereof
CA2628113A1 (en) 2005-11-04 2007-05-18 Nastech Pharmaceutical Company Inc. Peptide-dicer substrate rna conjugates as delivery vehicles for sirna
WO2007087451A2 (en) 2006-01-25 2007-08-02 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
JPWO2007094218A1 (ja) 2006-02-16 2009-07-02 国立大学法人岐阜大学 修飾オリゴヌクレオチド
EP1986697B1 (en) 2006-02-17 2016-06-29 GE Healthcare 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
EP2046993A4 (en) 2006-07-07 2010-11-17 Univ Massachusetts RNA SILENCING COMPOSITIONS, AND METHODS OF TREATING HUNTINGTON CHOREA
US20080039415A1 (en) 2006-08-11 2008-02-14 Gregory Robert Stewart Retrograde transport of sirna and therapeutic uses to treat neurologic disorders
WO2008036841A2 (en) 2006-09-22 2008-03-27 Dharmacon, Inc. Tripartite 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
TW200836762A (en) 2006-11-27 2008-09-16 Enzon Pharmaceuticals Inc Polymeric short interfering RNA conjugates
CA2679342A1 (en) 2007-03-02 2008-09-12 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
US20110046206A1 (en) 2007-06-22 2011-02-24 Isis Pharmaceuticals, Inc. Double strand compositions comprising differentially modified strands for use in gene modulation
JP2010537640A (ja) 2007-08-27 2010-12-09 ボストン バイオメディカル， インコーポレイテッド マイクロｒｎａ模倣剤または阻害剤としての非対称性ｒｎａ二重鎖の組成物
CN101199858A (zh) 2007-10-18 2008-06-18 广州拓谱基因技术有限公司 治疗眼科疾病的多靶点小干扰rna鸡尾酒制剂及制备方法
TW200927177A (en) 2007-10-24 2009-07-01 Nat Inst Of Advanced Ind Scien Lipid-modified double-stranded RNA having potent RNA interference effect
WO2009082607A2 (en) 2007-12-04 2009-07-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
US9029524B2 (en) 2007-12-10 2015-05-12 California Institute Of Technology Signal activated RNA interference
US20110081362A1 (en) 2008-01-31 2011-04-07 The Brigham And Women's Hospital, Inc. Treatment of cancer
US10131904B2 (en) 2008-02-11 2018-11-20 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
EP2318528A1 (en) 2008-07-24 2011-05-11 Rxi Pharmaceuticals Corporation Rnai constructs and uses therof
US20110223665A1 (en) 2008-07-25 2011-09-15 Alnylam Pharmaceuticals, Inc. ENHANCEMENT OF siRNA SILENCING ACTIVITY USING UNIVERSAL BASES OR MISMATCHES IN THE SENSE STRAND
CA2746527A1 (en) 2008-09-22 2010-03-25 Rxi Pharmaceuticals Corporation Rna interference in skin indications
DK2337860T3 (en) 2008-10-15 2016-08-29 Axolabs Gmbh A method for the detection of oligonucleotides
EP2358398A2 (en) 2008-10-24 2011-08-24 Isis Pharmaceuticals, Inc. Oligomeric compounds and methods
WO2010059226A2 (en) 2008-11-19 2010-05-27 Rxi Pharmaceuticals Corporation Inhibition of map4k4 through rnai
US9493774B2 (en) 2009-01-05 2016-11-15 Rxi Pharmaceuticals Corporation Inhibition of PCSK9 through RNAi
CA2750561C (en) 2009-01-26 2017-10-10 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
WO2010118263A1 (en) 2009-04-08 2010-10-14 University Of Massachusetts Single-nucleotide polymorphism (snp) targeting therapies for the treatment of huntington's disease
WO2010138263A2 (en) 2009-05-28 2010-12-02 University Of Massachusetts Novel aav 's and uses thereof
GB0910723D0 (en) 2009-06-22 2009-08-05 Sylentis Sau Novel drugs for inhibition of gene expression
DK2470656T3 (da) 2009-08-27 2015-06-22 Idera Pharmaceuticals Inc Sammensætning til hæmning af genekspression og anvendelser heraf
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
WO2011109698A1 (en) 2010-03-04 2011-09-09 Rxi Pharmaceuticals Corporation Formulations and methods for targeted delivery to phagocyte cells
US9080171B2 (en) 2010-03-24 2015-07-14 RXi Parmaceuticals Corporation Reduced size self-delivering RNAi compounds
BR112012024049A2 (pt) 2010-03-24 2017-03-01 Rxi Pharmaceuticals Corp interferência de rna em indicações dérmicas e fibróticas
CN106074591B (zh) 2010-03-24 2020-01-14 菲奥医药公司 眼部症候中的rna干扰
KR101869570B1 (ko) 2010-04-28 2018-06-20 아이오니스 파마수티컬즈, 인코포레이티드 변형된 뉴클레오사이드 및 그로부터 제조된 올리고머 화합물
WO2012005898A2 (en) 2010-06-15 2012-01-12 Alnylam Pharmaceuticals, Inc. Chinese hamster ovary (cho) cell transcriptome, corresponding sirnas and uses thereof
US8586301B2 (en) 2010-06-30 2013-11-19 Stratos Genomics, Inc. Multiplexed identification of nucleic acid sequences
CA2812046A1 (en) 2010-09-15 2012-03-22 Alnylam Pharmaceuticals, Inc. Modified irna agents
WO2012078637A2 (en) 2010-12-06 2012-06-14 Immune Disease Institute, Inc. Composition and method for oligonucleotide delivery
EP2652134B1 (en) 2010-12-17 2017-03-01 Arrowhead Pharmaceuticals, Inc. Galactose cluster-pharmacokinetic modulator targeting moiety for sirna
CN103562387A (zh) 2011-03-03 2014-02-05 夸克医药公司 Toll样受体途径的寡核苷酸调剂
US20140275211A1 (en) 2011-06-21 2014-09-18 Alnylam Pharmaceuticals, Inc. Assays and methods for determining activity of a therapeutic agent in a subject
WO2013165816A2 (en) 2012-05-02 2013-11-07 Merck Sharp & Dohme Corp. SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS
CN108148838A (zh) 2012-05-22 2018-06-12 奥利克斯医药有限公司 具有细胞内穿透能力的诱导rna干扰的核酸分子及用途
CA2877985C (en) 2012-07-10 2020-10-27 Baseclick Gmbh Anandamide-modified nucleic acid molecules
EP2895200B1 (en) 2012-09-14 2019-11-06 Translate Bio MA, 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
US10077443B2 (en) 2012-11-15 2018-09-18 Roche Innovation Center Copenhagen A/S Oligonucleotide conjugates
US10125369B2 (en) 2012-12-05 2018-11-13 Alnylam Pharmaceuticals, Inc. PCSK9 iRNA compositions and methods of use thereof
US20140200124A1 (en) 2013-01-15 2014-07-17 Karen Michelle JAMES Physical Therapy Device and Methods for Use Thereof
DK2991656T3 (da) 2013-05-01 2020-03-23 Ionis Pharmaceuticals Inc Sammensætninger og fremgangsmåder til modulering af apolipoprotein c-iii-ekspression
CN105324119A (zh) 2013-06-16 2016-02-10 国立大学法人东京医科齿科大学 具有外显子跳跃效应的双链反义核酸
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
WO2015057847A1 (en) 2013-10-16 2015-04-23 Cerulean Pharma Inc. Conjugates, particles, compositions, and related methods
WO2015070173A1 (en) 2013-11-08 2015-05-14 Isis Pharmaceuticals, Inc. Compounds and methods for detecting oligonucleotides
EP3733856A1 (en) 2014-04-18 2020-11-04 University of Massachusetts Exosomal loading using hydrophobically modified oligonucleotides
WO2015168661A1 (en) 2014-05-01 2015-11-05 Smith Larry J METHODS AND MODIFICATIONS THAT PRODUCE ssRNAi COMPOUNDS WITH ENHANCED ACTIVITY, POTENCY AND DURATION OF EFFECT
CA3215908A1 (en) 2014-05-22 2015-11-26 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
WO2016055601A1 (en) 2014-10-10 2016-04-14 F. Hoffmann-La Roche Ag Galnac phosphoramidites, nucleic acid conjugates thereof and their use
WO2016083623A1 (en) * 2014-11-28 2016-06-02 Silence Therapeutics Gmbh Means for the treatment of pre-eclampsia
JP2018509913A (ja) 2015-03-17 2018-04-12 アローヘッド ファーマシューティカルズ インコーポレイテッド 第ｘｉｉ因子の遺伝子発現を阻害するための組成物と方法
SMT202000454T1 (it) 2015-04-03 2020-11-10 Univ Massachusetts Cmposti oligonucleotidici per bersagliare l'mrn della huntingtina
PT3277815T (pt) 2015-04-03 2021-11-11 Beth Israel Deaconess Medical Ct Inc Compostos de oligonucleótidos para o tratamento de pré-eclâmpsia e outros distúrbios angiogénicos
EP3277811B1 (en) 2015-04-03 2020-12-23 University of Massachusetts Fully stabilized asymmetric sirna
AU2016246820B2 (en) 2015-04-10 2021-08-12 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
CN108135921B (zh) 2015-07-22 2023-10-17 波涛生命科学有限公司 寡核苷酸组合物及其方法
WO2017024239A1 (en) 2015-08-06 2017-02-09 City Of Hope Therapeutic cell internalizing conjugates
US10633653B2 (en) 2015-08-14 2020-04-28 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
JP7511326B2 (ja) 2015-10-09 2024-07-05 ウェイブ ライフ サイエンシズ リミテッド オリゴヌクレオチド組成物およびその方法
CN105194689A (zh) 2015-10-10 2015-12-30 湖南中楚博生物科技有限公司 一种基于siRNA的双偶联复合物
WO2017132669A1 (en) 2016-01-31 2017-08-03 University Of Massachusetts Branched oligonucleotides
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
WO2017174572A1 (en) 2016-04-04 2017-10-12 F. Hoffmann-La Roche Ag Nucleic acid sample preparation methods
CA3033368A1 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
JP7155239B2 (ja) 2017-04-05 2022-10-18 サイレンス・セラピューティクス・ゲーエムベーハー 産物及び組成物
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
CA3071086A1 (en) 2017-08-18 2019-02-21 The Procter & Gamble Company Cleaning agent
EP3550021A1 (en) 2018-04-05 2019-10-09 Silence Therapeutics GmbH Products and compositions for inhibiting expression of a target gene
WO2020033899A1 (en) 2018-08-10 2020-02-13 University Of Massachusetts Modified oligonucleotides targeting snps
JP7627042B2 (ja) 2018-08-23 2025-02-05 ユニバーシティー オブ マサチューセッツ Ｏ－メチルリッチ完全安定化オリゴヌクレオチド
CN113614232A (zh) 2019-01-18 2021-11-05 马萨诸塞大学 动态药代动力学修饰锚
US11820985B2 (en) 2019-03-26 2023-11-21 University Of Massachusetts Modified oligonucleotides with increased stability
JP2022545118A (ja) 2019-08-23 2022-10-25 ユニバーシティー オブ マサチューセッツ Ｏ－メチルリッチ完全安定化オリゴヌクレオチド
GB201914296D0 (en) 2019-10-03 2019-11-20 Univ Oxford Innovation Ltd Treatment
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
WO2021242883A1 (en) 2020-05-26 2021-12-02 University Of Massachusetts Synthetic oligonucleotides having regions of block and cluster modifications
JP2023550485A (ja) 2020-11-23 2023-12-01 ユニバーシティー オブ マサチューセッツ Ｄｇａｔ２調節のためのオリゴヌクレオチド

Also Published As

Publication number Publication date
JP2026009427A (ja) 2026-01-20
AU2022299169A1 (en) 2024-02-08
IL309334A (en) 2024-02-01
WO2022271786A1 (en) 2022-12-29
AR126207A1 (es) 2023-09-27
JP2024523509A (ja) 2024-06-28
US20240067967A1 (en) 2024-02-29
US11702659B2 (en) 2023-07-18
EP4359539A4 (en) 2025-05-14
MX2023015523A (es) 2024-03-11
CA3174095A1 (en) 2022-12-29
KR20240040729A (ko) 2024-03-28
EP4359539A1 (en) 2024-05-01
CN117677699A (zh) 2024-03-08
JP7758907B2 (ja) 2025-10-23
US20230078622A1 (en) 2023-03-16
BR112023026862A2 (pt) 2024-03-05

Similar Documents

Publication Publication Date Title
JP7758907B2 (ja) 子癇前症及び他の血管新生障害の治療のために最適化された抗ｆｌｔ１オリゴヌクレオチド化合物
US20220364100A1 (en) Oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
JP7504482B2 (ja) ハンチンチンｍＲＮＡをターゲティングするオリゴヌクレオチド化合物
JP7687685B2 (ja) 組織特異的なａｐｏｅ調節のためのオリゴヌクレオチド
US20210355491A1 (en) Oligonucleotides for msh3 modulation
JP2023550485A (ja) Ｄｇａｔ２調節のためのオリゴヌクレオチド
US20230313198A1 (en) Oligonucleotides for mlh3 modulation
AU2020252020A1 (en) Oligonucleotide-based modulation of C90RF72
US20230392146A1 (en) Oligonucleotides for app modulation
WO2021195510A1 (en) Dual-acting sirna based modulation of c9orf72
CN115777021A (zh) 用于snca调节的寡核苷酸
HK40074069A (en) Oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
CN117642508A (zh) 用于IFN-γ信号传导途径调节的寡核苷酸