CN113939592A - 导入了化学修饰核酸的稳定型目标编辑向导rna - Google Patents

导入了化学修饰核酸的稳定型目标编辑向导rna Download PDF

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Publication number
CN113939592A
CN113939592A CN202080041457.0A CN202080041457A CN113939592A CN 113939592 A CN113939592 A CN 113939592A CN 202080041457 A CN202080041457 A CN 202080041457A CN 113939592 A CN113939592 A CN 113939592A
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oligonucleotide
residue
pharmaceutically acceptable
acceptable salt
target
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Chinese (zh)
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福田将虎
小泉诚
岩下真三
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Daiichi Sankyo Co Ltd
Fukuoka University
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Daiichi Sankyo Co Ltd
Fukuoka University
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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    • C—CHEMISTRY; METALLURGY
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    • C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
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    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/318—Chemical structure of the backbone where the PO2 is completely replaced, e.g. MMI or formacetal
    • C12N2310/3183—Diol linkers, e.g. glycols or propanediols
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    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
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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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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
CN202080041457.0A 2019-06-05 2020-06-04 导入了化学修饰核酸的稳定型目标编辑向导rna Pending CN113939592A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
JP2019-105532 2019-06-05
JP2019105532 2019-06-05
JP2019-148463 2019-08-13
JP2019148463 2019-08-13
PCT/JP2020/022200 WO2020246560A1 (ja) 2019-06-05 2020-06-04 化学修飾核酸を導入した安定型標的編集ガイドｒｎａ

Publications (1)

Publication Number Publication Date
CN113939592A true CN113939592A (zh) 2022-01-14

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CN202080041457.0A Pending CN113939592A (zh) 2019-06-05 2020-06-04 导入了化学修饰核酸的稳定型目标编辑向导rna

Country Status (11)

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US (1) US20230061732A1 (https=)
EP (1) EP3981436A4 (https=)
JP (1) JP7776076B2 (https=)
KR (1) KR20220016876A (https=)
CN (1) CN113939592A (https=)
AU (1) AU2020287787A1 (https=)
BR (1) BR112021024373A2 (https=)
CA (1) CA3140438A1 (https=)
IL (1) IL288633A (https=)
TW (1) TW202113076A (https=)
WO (1) WO2020246560A1 (https=)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017220751A1 (en) 2016-06-22 2017-12-28 Proqr Therapeutics Ii B.V. Single-stranded rna-editing 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
GB201808146D0 (en) 2018-05-18 2018-07-11 Proqr Therapeutics Ii Bv Stereospecific Linkages in RNA Editing Oligonucleotides
AU2020395113A1 (en) 2019-12-02 2022-06-09 Shape Therapeutics Inc. Therapeutic editing
US20240247258A1 (en) * 2020-03-12 2024-07-25 Frest Inc. Oligonucleotide and target rna site-specific editing method
MX2023006714A (es) * 2020-12-08 2023-07-13 Univ Fukuoka Acido ribonucleico (arn) guia estable de edicion de objetivo al cual se introduce acido nucleico quimicamente modificado.
EP4479535A1 (en) 2022-02-14 2024-12-25 ProQR Therapeutics II B.V. Guide oligonucleotides for nucleic acid editing in the treatment of hypercholesterolemia
US20260027237A1 (en) 2022-07-15 2026-01-29 Proqr Therapeutics Ii B.V. Chemically modified oligonucleotides for adar-mediated rna editing
JP2025524566A (ja) 2022-07-15 2025-07-30 プロキューアール セラピューティクス ツー ベスローテン フェンノートシャップ Ａｄａｒ媒介ｒｎａ編集のためのオリゴヌクレオチドおよびその使用
GB202215614D0 (en) 2022-10-21 2022-12-07 Proqr Therapeutics Ii Bv Heteroduplex rna editing oligonucleotide complexes
WO2024110565A1 (en) 2022-11-24 2024-05-30 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of hereditary hfe-hemochromatosis
WO2024114908A1 (en) * 2022-11-30 2024-06-06 Eberhard Karls Universität Tübingen Chemically modified antisense oligonucleotides (asos) and compositions comprising the same for rna editing
GB202218090D0 (en) 2022-12-01 2023-01-18 Proqr Therapeutics Ii Bv Antisense oligonucleotides for the treatment of aldehyde dehydrogenase 2 deficiency
AU2023390632A1 (en) 2022-12-09 2025-07-10 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of cardiovascular disease
GB202300865D0 (en) 2023-01-20 2023-03-08 Proqr Therapeutics Ii Bv Delivery of oligonucleotides
WO2024175550A1 (en) 2023-02-20 2024-08-29 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of atherosclerotic cardiovascular disease
EP4689110A1 (en) 2023-03-24 2026-02-11 ProQR Therapeutics II B.V. Antisense oligonucleotides for the treatment of neurological disorders
GB202304363D0 (en) 2023-03-24 2023-05-10 Proqr Therapeutics Ii Bv Chemically modified antisense oligonucleotides for use in RNA editing
EP4688143A1 (en) 2023-03-27 2026-02-11 ProQR Therapeutics II B.V. Antisense oligonucleotides for the treatment of liver disease
TW202516003A (zh) 2023-06-16 2025-04-16 荷蘭商Ｐｒｏｑｒ治療上市公司Ｉｉ 用於治療神經退化性疾病之反義寡核苷酸
WO2025047679A1 (ja) 2023-08-25 2025-03-06 学校法人福岡大学 リン酸部修飾を導入した安定型標的編集ガイドｒｎａ
WO2025051946A1 (en) 2023-09-07 2025-03-13 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of metabolic disorders
WO2025104239A1 (en) 2023-11-16 2025-05-22 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of classic galactosemia
WO2025132708A1 (en) 2023-12-20 2025-06-26 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of huntington's disease
GB202404661D0 (en) 2024-04-02 2024-05-15 Proqr Therapeutics Ii Bv Antisense oligoncleotides for the treatment of liver disease
WO2025224230A1 (en) 2024-04-25 2025-10-30 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of fatty liver disease
GB202410081D0 (en) 2024-07-11 2024-08-28 Proqr Therapeutics Ii Bv Antisense oligonucleotides for the treatment of cardiovascular disease
WO2026022136A1 (en) 2024-07-23 2026-01-29 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of metabolic disorders
WO2026060374A2 (en) 2024-09-16 2026-03-19 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of neurological disorders
WO2026068781A1 (en) 2024-09-30 2026-04-02 Proqr Therapeutics Ii B.V. Antisense oligonucleotides for the treatment of liver disease

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107109413A (zh) * 2014-12-17 2017-08-29 ProQR治疗上市公司Ⅱ 靶向的rna编辑
US20180208924A1 (en) * 2015-07-14 2018-07-26 Fukuoka University Method for introducing site-directed rna mutation, target editing guide rna used in the method and target rna-target editing guide rna complex
CN109477103A (zh) * 2016-06-22 2019-03-15 ProQR治疗上市公司Ⅱ 单链rna-编辑寡核苷酸
WO2019111957A1 (ja) * 2017-12-06 2019-06-13 学校法人福岡大学 オリゴヌクレオチド、その製造方法及び標的ｒｎａの部位特異的編集方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6096881A (en) 1997-05-30 2000-08-01 Hybridon, Inc. Sulfur transfer reagents for oligonucleotide synthesis
JP4236812B2 (ja) 1997-09-12 2009-03-11 エクシコン エ／エス オリゴヌクレオチド類似体
US9150605B2 (en) 2002-11-05 2015-10-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2′-modified nucleosides for use in gene modulation
US20160319278A1 (en) 2015-04-03 2016-11-03 University Of Massachusetts Fully stabilized asymmetric sirna
CA3205381A1 (en) 2015-07-17 2017-01-26 Alnylam Pharmaceuticals, Inc. Multi-targeted single entity conjugates
SK500652015A3 (sk) 2015-10-15 2017-05-03 Ústav Polymérov Sav Spôsob úpravy funkčného stavu ľubovoľnej mRNA umožňujúci jej selektívne a špecifické rozpoznanie
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
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

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107109413A (zh) * 2014-12-17 2017-08-29 ProQR治疗上市公司Ⅱ 靶向的rna编辑
US20180208924A1 (en) * 2015-07-14 2018-07-26 Fukuoka University Method for introducing site-directed rna mutation, target editing guide rna used in the method and target rna-target editing guide rna complex
CN109477103A (zh) * 2016-06-22 2019-03-15 ProQR治疗上市公司Ⅱ 单链rna-编辑寡核苷酸
WO2019111957A1 (ja) * 2017-12-06 2019-06-13 学校法人福岡大学 オリゴヌクレオチド、その製造方法及び標的ｒｎａの部位特異的編集方法

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BR112021024373A2 (pt) 2022-01-18
WO2020246560A1 (ja) 2020-12-10
JPWO2020246560A1 (https=) 2020-12-10
US20230061732A1 (en) 2023-03-02
TW202113076A (zh) 2021-04-01
CA3140438A1 (en) 2020-12-10
AU2020287787A1 (en) 2022-01-20
EP3981436A4 (en) 2024-06-19
IL288633A (en) 2022-02-01
JP7776076B2 (ja) 2025-11-26
KR20220016876A (ko) 2022-02-10
EP3981436A1 (en) 2022-04-13

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