CN116600817A - 用于组织特异性递送的缀合寡核苷酸 - Google Patents

用于组织特异性递送的缀合寡核苷酸 Download PDF

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Publication number
CN116600817A
CN116600817A CN202180061336.7A CN202180061336A CN116600817A CN 116600817 A CN116600817 A CN 116600817A CN 202180061336 A CN202180061336 A CN 202180061336A CN 116600817 A CN116600817 A CN 116600817A
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Prior art keywords
nucleotides
sirna
nucleotide
modified
antisense strand
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CN202180061336.7A
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English (en)
Chinese (zh)
Inventor
阿纳斯塔西娅·科沃罗娃
安娜贝尔·比斯坎斯
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University of Massachusetts Amherst
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University of Massachusetts Amherst
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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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
    • 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
    • C12N15/111—General methods applicable to biologically active non-coding 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
    • A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
    • 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
    • C12N2310/315—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
    • C12N2310/34—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
    • C12N2320/00—Applications; Uses
    • C12N2320/30—Special therapeutic applications
    • C12N2320/32—Special delivery means, e.g. tissue-specific
    • 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
    • C12N2320/50—Methods for regulating/modulating their activity

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Public Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN202180061336.7A 2020-07-16 2021-07-16 用于组织特异性递送的缀合寡核苷酸 Pending CN116600817A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202063052811P 2020-07-16 2020-07-16
US63/052,811 2020-07-16
PCT/US2021/041946 WO2022016043A1 (en) 2020-07-16 2021-07-16 Conjugated oligonucleotides for tissue specific delivery

Publications (1)

Publication Number Publication Date
CN116600817A true CN116600817A (zh) 2023-08-15

Family

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Family Applications (1)

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CN202180061336.7A Pending CN116600817A (zh) 2020-07-16 2021-07-16 用于组织特异性递送的缀合寡核苷酸

Country Status (7)

Country Link
US (1) US20220042015A1 (https=)
EP (1) EP4181932A4 (https=)
JP (1) JP2023534951A (https=)
CN (1) CN116600817A (https=)
AU (1) AU2021308657A1 (https=)
CA (1) CA3174068A1 (https=)
WO (1) WO2022016043A1 (https=)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA3033368A1 (en) * 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
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
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
US12366070B2 (en) 2021-04-23 2025-07-22 Stephen Cochran Cover for circular-profile downspouts having protection from animal/insect intrusion and damage/debris accumulation
IL317825A (en) 2022-07-25 2025-02-01 Amgen Inc RNA interference constructs and methods for inhibiting fam13a expression
US20260049309A1 (en) * 2022-08-15 2026-02-19 Novo Nordisk A/S Regulation of activity of rnai molecules
WO2024069235A2 (en) 2022-09-30 2024-04-04 Sixfold Bioscience Ltd. Compositions containing oligonucleotides with theranostic applications
WO2025217569A1 (en) * 2024-04-11 2025-10-16 University Of Massachusetts Conjugated chemically-modified dsrna during ex vivo perfusion of organs
WO2025259747A2 (en) * 2024-06-12 2025-12-18 Alnylam Pharmaceuticals, Inc. Dystrophy myotonic protein kinase (dmpk) irna compositions and methods of use thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018031933A2 (en) * 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
WO2019217459A1 (en) * 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9745574B2 (en) * 2009-02-04 2017-08-29 Rxi Pharmaceuticals Corporation RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
EP3517610A4 (en) * 2016-09-23 2020-05-27 National University Corporation Tokyo Medical and Dental University THROUGH HETERODUPLEX NUCLEIC ACID THROUGH BLOOD BRAIN CABINET
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

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018031933A2 (en) * 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
WO2019217459A1 (en) * 2018-05-07 2019-11-14 Alnylam Pharmaceuticals, Inc. Extrahepatic delivery

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
MICHAEL E. ØSTERGAARD等: "Conjugation of hydrophobic moieties enhances potency of antisense oligonucleotides in the muscle of rodents and non-human primates", NUCLEIC ACIDS RESEARCH, vol. 47, no. 12, 11 May 2019 (2019-05-11), pages 6045 - 6058, XP055871629, DOI: 10.1093/nar/gkz360 *

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Publication number Publication date
EP4181932A4 (en) 2025-07-16
CA3174068A1 (en) 2022-01-20
AU2021308657A1 (en) 2023-03-02
US20220042015A1 (en) 2022-02-10
JP2023534951A (ja) 2023-08-15
WO2022016043A1 (en) 2022-01-20
EP4181932A1 (en) 2023-05-24

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