CA3190097A1 - Modified sirna with reduced off-target activity - Google Patents

Modified sirna with reduced off-target activity

Info

Publication number
CA3190097A1
CA3190097A1 CA3190097A CA3190097A CA3190097A1 CA 3190097 A1 CA3190097 A1 CA 3190097A1 CA 3190097 A CA3190097 A CA 3190097A CA 3190097 A CA3190097 A CA 3190097A CA 3190097 A1 CA3190097 A1 CA 3190097A1
Authority
CA
Canada
Prior art keywords
group
methoxy
alkyl
alkynyl
alkenyl
Prior art date
Legal status (The legal status 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 status listed.)
Pending
Application number
CA3190097A
Other languages
English (en)
French (fr)
Inventor
Jinyu Huang
Min Luo
Ke YIN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tuojie Biotech Shanghai Co Ltd
Original Assignee
Tuojie Biotech Shanghai Co Ltd
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 Tuojie Biotech Shanghai Co Ltd filed Critical Tuojie Biotech Shanghai Co Ltd
Publication of CA3190097A1 publication Critical patent/CA3190097A1/en
Pending legal-status Critical Current

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    • 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
    • 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
    • C12N15/1131—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 viruses
    • 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
    • C12N15/1136—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 growth factors, growth regulators, cytokines, lymphokines or hormones
    • 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
    • C12N2310/313—Phosphorodithioates
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/319—Chemical structure of the backbone linked by 2'-5' linkages, i.e. having a free 3'-position
    • 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
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • 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
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3235—Chemical structure of the sugar modified ring structure having the O of the ribose replaced by another atom
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/33—Chemical structure of the base
    • 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
    • C12N2310/33—Chemical structure of the base
    • C12N2310/332—Abasic residue
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • C12N2310/3513—Protein; Peptide
    • 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
    • C12N2320/53—Methods for regulating/modulating their activity reducing unwanted side-effects

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (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)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
CA3190097A 2020-08-04 2021-08-04 Modified sirna with reduced off-target activity Pending CA3190097A1 (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
CN202010772542.6 2020-08-04
CN202010772542 2020-08-04
CN202110244977.8 2021-03-05
CN202110244977 2021-03-05
CN202110361502 2021-04-02
CN202110361502.7 2021-04-02
PCT/CN2021/110509 WO2022028462A1 (zh) 2020-08-04 2021-08-04 脱靶活性降低的修饰sirna

Publications (1)

Publication Number Publication Date
CA3190097A1 true CA3190097A1 (en) 2022-02-10

Family

ID=80120017

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3190097A Pending CA3190097A1 (en) 2020-08-04 2021-08-04 Modified sirna with reduced off-target activity

Country Status (10)

Country Link
US (1) US20230287418A1 (enExample)
EP (1) EP4194553A4 (enExample)
JP (1) JP7849353B2 (enExample)
KR (1) KR20230043195A (enExample)
CN (1) CN115955973A (enExample)
BR (1) BR112023002080A2 (enExample)
CA (1) CA3190097A1 (enExample)
TW (1) TW202214858A (enExample)
WO (1) WO2022028462A1 (enExample)
ZA (1) ZA202303275B (enExample)

Cited By (1)

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JP2026503329A (ja) * 2023-02-21 2026-01-28 成都先導薬物開発股▲フン▼有限公司 ヌクレオチド類似体、その調製方法及び使用

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WO2022206946A1 (zh) * 2021-04-02 2022-10-06 上海拓界生物医药科技有限公司 乙型肝炎病毒siRNA和siRNA缀合物
EP4328310A4 (en) * 2021-04-22 2025-10-15 Tuojie Biotech Shanghai Co Ltd SIRNA TARGETING 17β-HYDROXYSTEROID DEHYDROGENASE TYPE 13 AND SIRNA CONJUGATE
WO2023109932A1 (zh) * 2021-12-16 2023-06-22 上海拓界生物医药科技有限公司 一种dsRNA、其制备方法及应用
TW202340469A (zh) 2022-01-20 2023-10-16 大陸商上海拓界生物醫藥科技有限公司 一種ｄｓｒｎａ、其應用及製備方法
EP4635967A1 (en) * 2022-12-13 2025-10-22 Tuojie Biotech (Shanghai) Co., Ltd. Oligonucleotide comprising lipophilic monomer and use thereof in non-liver delivery
US20260234620A1 (en) 2023-03-02 2026-08-13 Tuojie Biotech (Shanghai) Co., Ltd. siRNA Targeting Inhibin BetaE, siRNA Conjugate, And Medical Use Thereof
AU2024258620A1 (en) * 2023-04-21 2025-11-06 Suzhou Siran Biotechnology Co., Ltd. Oligomeric nucleic acid, and preparation method therefore and use thereof
TW202442243A (zh) 2023-04-27 2024-11-01 大陸商上海森輝醫藥有限公司 用於製備寡核苷酸類似物或其鹽的中間體及其製備方法
KR20260020955A (ko) 2023-05-31 2026-02-12 투오지에 바이오텍 (상하이) 컴퍼니 리미티드 LPA를 표적화하는 dsRNA 및 이의 응용
MX2025014897A (es) 2023-06-13 2026-02-03 Tuojie Biotech Shanghai Co Ltd Arnip dirigido a mmp7, conjugado de arnip y su uso medico
WO2025007907A1 (zh) * 2023-07-04 2025-01-09 大睿生物 包含肽的寡核苷酸递送配体
KR20260046111A (ko) 2023-08-01 2026-04-06 투오지에 바이오텍 (상하이) 컴퍼니 리미티드 MAPT를 표적으로 하는 dsRNA 및 이의 의약적 용도
CN121586578A (zh) 2023-08-24 2026-02-27 上海拓界生物医药科技有限公司 靶向RAGE的RNAi剂及其医药用途
KR20260089666A (ko) * 2023-09-14 2026-06-15 아이오니스 파마수티컬즈, 인코포레이티드 Apociii 발현을 감소시키기 위한 화합물 및 방법
WO2025067317A1 (zh) * 2023-09-26 2025-04-03 上海拓界生物医药科技有限公司 一种脂质修饰的核酸化合物、其制备方法及用途
CN120209036A (zh) * 2023-12-26 2025-06-27 广东东阳光药业股份有限公司 一种新型的化合物及其用途
WO2026002138A1 (zh) * 2024-06-27 2026-01-02 成都新泽利医药科技有限公司 特定修饰的双链寡核苷酸及其组合物
CN121175422A (zh) * 2024-10-08 2025-12-19 北京安龙生物医药有限公司 修饰的双链寡核苷酸及其缀合物和组合物
CN119410644A (zh) * 2025-01-08 2025-02-11 北京安龙生物医药有限公司 修饰的双链寡核苷酸及其缀合物和组合物
CN119528986B (zh) * 2025-01-23 2025-09-16 北京悦康科创医药科技股份有限公司 一种核苷类似物及其在降低寡核苷酸药物脱靶活性中的应用

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EP4328310A4 (en) 2021-04-22 2025-10-15 Tuojie Biotech Shanghai Co Ltd SIRNA TARGETING 17β-HYDROXYSTEROID DEHYDROGENASE TYPE 13 AND SIRNA CONJUGATE

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2026503329A (ja) * 2023-02-21 2026-01-28 成都先導薬物開発股▲フン▼有限公司 ヌクレオチド類似体、その調製方法及び使用

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ZA202303275B (en) 2025-12-17
TW202214858A (zh) 2022-04-16
EP4194553A4 (en) 2024-11-13
EP4194553A1 (en) 2023-06-14
US20230287418A1 (en) 2023-09-14
JP2023536320A (ja) 2023-08-24
WO2022028462A1 (zh) 2022-02-10
JP7849353B2 (ja) 2026-04-21
BR112023002080A2 (pt) 2023-04-25
KR20230043195A (ko) 2023-03-30
CN115955973A (zh) 2023-04-11

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