CN114761557B - 具有最小氟含量的小干扰rna的化学修饰 - Google Patents

具有最小氟含量的小干扰rna的化学修饰 Download PDF

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CN114761557B
CN114761557B CN202080082980.8A CN202080082980A CN114761557B CN 114761557 B CN114761557 B CN 114761557B CN 202080082980 A CN202080082980 A CN 202080082980A CN 114761557 B CN114761557 B CN 114761557B
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modified
antisense strand
nucleotides
oligonucleotide
positions
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CN114761557A (zh
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W·王
N·纳泽夫
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Novo Nordisk AS
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Dicerna Pharmaceuticals Inc
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    • 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
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    • 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
    • C12N15/1137—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 enzymes
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    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed
    • C12N2310/533—Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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CN202080082980.8A 2019-10-02 2020-10-02 具有最小氟含量的小干扰rna的化学修饰 Active CN114761557B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201962909278P 2019-10-02 2019-10-02
US62/909278 2019-10-02
PCT/US2020/053999 WO2021067744A1 (en) 2019-10-02 2020-10-02 Chemical modifications of small interfering rna with minimal fluorine content

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CN114761557A CN114761557A (zh) 2022-07-15
CN114761557B true CN114761557B (zh) 2024-11-15

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US (1) US20220389430A1 (https=)
EP (1) EP4038191A1 (https=)
JP (1) JP2022551269A (https=)
KR (1) KR20220069103A (https=)
CN (1) CN114761557B (https=)
AU (1) AU2020358016A1 (https=)
CA (1) CA3153026A1 (https=)
CL (1) CL2022000825A1 (https=)
IL (1) IL291841A (https=)
MX (1) MX2022004032A (https=)
TW (1) TW202126809A (https=)
WO (1) WO2021067744A1 (https=)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4323518A2 (en) 2021-04-12 2024-02-21 Boehringer Ingelheim International GmbH Compositions and methods for inhibiting ketohexokinase (khk)
US12084662B2 (en) * 2021-04-14 2024-09-10 Dicerna Pharmaceuticals, Inc. Compositions and methods for modulating PNPLA3 expression
CN117580953B (zh) * 2021-07-16 2025-07-18 苏州瑞博生物技术股份有限公司 一种核酸、含有该核酸的组合物与缀合物及制备方法和用途
EP4405368A1 (en) * 2021-09-22 2024-07-31 Sanegene Bio USA Inc. 2'-alkyl or 3'- alkyl modified ribose derivatives for use in the in-vivo delivery of oligonucleotides
US20250223588A1 (en) * 2021-10-19 2025-07-10 Alnylam Pharmaceuticals, Inc. Oligonucleotides with 2'-deoxy-2'-f-2'-c-methyl nucleotides
WO2023102469A2 (en) 2021-12-01 2023-06-08 Dicerna Pharmaceuticals, Inc. Compositions and methods for modulating apoc3 expression
WO2023208023A1 (zh) * 2022-04-26 2023-11-02 上海拓界生物医药科技有限公司 氘代化学修饰和包含其的寡核苷酸
TW202526017A (zh) * 2023-09-14 2025-07-01 美商Ionis製藥公司 用於減少ａｐｏｃｉｉｉ表現的化合物及方法
WO2025191337A2 (en) * 2024-03-11 2025-09-18 Synerk Biotech Limited Oligonucleotide terminal phosphate derivatives and method of use

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019079781A2 (en) * 2017-10-20 2019-04-25 Dicerna Pharmaceuticals, Inc METHODS OF TREATING HEPATITIS B TYPE INFECTIONS

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040259247A1 (en) 2000-12-01 2004-12-23 Thomas Tuschl Rna interference mediating small rna molecules
JP2005508196A (ja) 2001-11-07 2005-03-31 アプレラ コーポレイション 核酸分析の汎用ヌクレオチド
US20070265220A1 (en) 2004-03-15 2007-11-15 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
WO2007030167A1 (en) 2005-09-02 2007-03-15 Nastech Pharmaceutical Company Inc. Modification of double-stranded ribonucleic acid molecules
JP2012504389A (ja) 2008-09-22 2012-02-23 ダイセルナ ファーマシューティカルズ， インコーポレイテッド 修飾を有するｄｓＲＮＡによる遺伝子発現の特異的な阻害のための組成物および方法
US8691971B2 (en) 2008-09-23 2014-04-08 Scott G. Petersen Self delivering bio-labile phosphate protected pro-oligos for oligonucleotide based therapeutics and mediating RNA interference
AU2009336191B2 (en) 2008-12-18 2017-08-24 Novo Nordisk A/S Extended dicer substrate agents and methods for the specific inhibition of gene expression
US20100249214A1 (en) 2009-02-11 2010-09-30 Dicerna Pharmaceuticals Multiplex dicer substrate rna interference molecules having joining sequences
US8927513B2 (en) 2009-07-07 2015-01-06 Alnylam Pharmaceuticals, Inc. 5′ phosphate mimics
WO2011133871A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. 5'-end derivatives
EP2928877B1 (en) 2012-12-06 2020-01-22 Merck Sharp & Dohme Corp. Disulfide masked prodrug compositions and methods
JP2017522046A (ja) 2014-06-06 2017-08-10 ソルスティス バイオロジクス，リミティッド 生物可逆的および生物不可逆的基を有するポリヌクレオチド構築物
JP7105065B2 (ja) 2014-12-15 2022-07-22 ダイセルナ ファーマシューティカルズ， インコーポレイテッド リガンド修飾二本鎖核酸
HRP20231063T1 (hr) * 2017-10-13 2023-12-22 Novo Nordisk Health Care Ag Postupci i pripravci namijenjeni inhibiranju eksprimiranja ldha

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019079781A2 (en) * 2017-10-20 2019-04-25 Dicerna Pharmaceuticals, Inc METHODS OF TREATING HEPATITIS B TYPE INFECTIONS

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JP2022551269A (ja) 2022-12-08
CL2022000825A1 (es) 2023-01-27
KR20220069103A (ko) 2022-05-26
MX2022004032A (es) 2022-09-21
CA3153026A1 (en) 2021-04-08
AU2020358016A1 (en) 2022-04-21
EP4038191A1 (en) 2022-08-10
TW202126809A (zh) 2021-07-16
WO2021067744A1 (en) 2021-04-08
IL291841A (en) 2022-06-01
US20220389430A1 (en) 2022-12-08
CN114761557A (zh) 2022-07-15

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