CN113811311A - 用于组织特异性apoe调节的寡核苷酸 - Google Patents

用于组织特异性apoe调节的寡核苷酸 Download PDF

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CN113811311A
CN113811311A CN202080036085.2A CN202080036085A CN113811311A CN 113811311 A CN113811311 A CN 113811311A CN 202080036085 A CN202080036085 A CN 202080036085A CN 113811311 A CN113811311 A CN 113811311A
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rna
compound
nucleotides
oligonucleotide
nucleotide
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阿纳斯塔西娅·赫沃罗娃
尚塔尔·弗格森
叶夫根尼·罗盖乌
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University of Massachusetts Amherst
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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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    • A—HUMAN NECESSITIES
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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  • Enzymes And Modification Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN202080036085.2A 2019-03-15 2020-03-13 用于组织特异性apoe调节的寡核苷酸 Pending CN113811311A (zh)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201962819189P 2019-03-15 2019-03-15
US62/819,189 2019-03-15
US201962864797P 2019-06-21 2019-06-21
US62/864,797 2019-06-21
US201962951441P 2019-12-20 2019-12-20
US62/951,441 2019-12-20
PCT/US2020/022748 WO2020190768A1 (en) 2019-03-15 2020-03-13 Oligonucleotides for tissue specific apoe modulation

Publications (1)

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CN113811311A true CN113811311A (zh) 2021-12-17

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CN202080036085.2A Pending CN113811311A (zh) 2019-03-15 2020-03-13 用于组织特异性apoe调节的寡核苷酸

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Country Link
US (1) US20200362341A1 (https=)
EP (1) EP3937951A4 (https=)
JP (2) JP7687685B2 (https=)
CN (1) CN113811311A (https=)
AU (1) AU2020239987A1 (https=)
CA (1) CA3133241A1 (https=)
WO (1) WO2020190768A1 (https=)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118460654A (zh) * 2024-07-10 2024-08-09 凯莱英医药集团（天津）股份有限公司 一种Givosiran的制备方法
WO2026057066A1 (zh) * 2024-09-14 2026-03-19 瑞典瑞博科尔制药公司 寡核苷酸、寡核苷酸缀合物及组合物和用途

Families Citing this family (19)

* 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
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
MX2022001710A (es) 2019-08-09 2022-05-10 Univ Massachusetts Oligonucleótidos modificados químicamente dirigidos a los snp.
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
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
KR20230018377A (ko) * 2020-04-27 2023-02-07 알닐람 파마슈티칼스 인코포레이티드 아포지질단백질 e (apoe) irna 제제 조성물 및 이의 사용 방법
WO2021242883A1 (en) 2020-05-26 2021-12-02 University Of Massachusetts Synthetic oligonucleotides having regions of block and cluster modifications
CN114716518A (zh) * 2021-01-06 2022-07-08 圣诺制药公司 一种能够抑制pcsk9表达的分子构造及药物组合物
WO2022187617A1 (en) * 2021-03-05 2022-09-09 Alnylam Pharmaceuticals, Inc. Dosing of sirna compounds to the cisterna magna
WO2022204430A1 (en) * 2021-03-24 2022-09-29 Atalanta Therapeutics, Inc. Double-stranded sirna having patterned chemical modifications
JP2024523466A (ja) * 2021-06-22 2024-06-28 ユニバーシティー オブ マサチューセッツ ＩＦＮ－γシグナル伝達経路の調節のためのオリゴヌクレオチド
WO2023086777A1 (en) * 2021-11-09 2023-05-19 Children's National Medical Center Targeting apoe enhances t-cell killing in cancer immunotherapy
US20240173420A1 (en) * 2022-09-30 2024-05-30 University Of Massachusetts Ocular delivery of oligonucleotides
WO2024233864A2 (en) * 2023-05-10 2024-11-14 Dicerna Pharmaceuticals, Inc. Galnac-conjugated rnai oligonucleotides
WO2025213111A2 (en) * 2024-04-05 2025-10-09 Cornell University Aav expression of mirna to suppress human apoe mrna
US20250353873A1 (en) * 2024-05-17 2025-11-20 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating apoe expression
WO2026067590A1 (zh) * 2024-09-27 2026-04-02 南京金斯瑞生物科技有限公司 修饰的双链rna分子

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060257851A1 (en) * 2002-11-26 2006-11-16 Itzhak Bentwich Bioinformatically detectable group of novel viral regulatory genes and uses thereof
US20080293655A1 (en) * 2006-02-08 2008-11-27 Huseyin Aygun Novel tandem siRNAS
EP2213738A2 (en) * 2002-11-14 2010-08-04 Dharmacon, Inc. siRNA molecules targeting Bcl-2
WO2013181618A2 (en) * 2012-05-31 2013-12-05 The Trustees Of Columbia University In The City Of New York Methods to treat alzheimer's disease using apoe inhibitors
US20150141320A1 (en) * 2012-05-16 2015-05-21 Rana Therapeutics, Inc. Compositions and methods for modulating gene expression
WO2017132669A1 (en) * 2016-01-31 2017-08-03 University Of Massachusetts Branched oligonucleotides
US20170334977A1 (en) * 2014-10-20 2017-11-23 The Brigham And Women's Hospital, Inc. Targeting Apolipoprotein E (APOE) in Neurologic Disease

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2643048A1 (en) 2006-02-21 2007-08-30 Oklahoma Medical Research Foundation Treatment of alzheimer's disease with inhibitors of apoe binding to apoe receptor
US8178503B2 (en) * 2006-03-03 2012-05-15 International Business Machines Corporation Ribonucleic acid interference molecules and binding sites derived by analyzing intergenic and intronic regions of genomes
WO2008021353A2 (en) 2006-08-14 2008-02-21 Guangxiang Luo Composition and method for controlling hepatitis c virus infection
JP5524189B2 (ja) * 2008-06-06 2014-06-18 クォーク ファーマシューティカルズ インコーポレーティッド 耳障害治療のための組成物および方法
CN102459596B (zh) * 2009-05-06 2016-09-07 库尔纳公司 通过针对脂质转运和代谢基因的天然反义转录物的抑制治疗脂质转运和代谢基因相关疾病
DK2470656T3 (da) 2009-08-27 2015-06-22 Idera Pharmaceuticals Inc Sammensætning til hæmning af genekspression og anvendelser heraf
KR101029699B1 (ko) 2010-09-29 2011-04-18 동국대학교 산학협력단 생약추출물을 유효성분으로 함유하는 알쯔하이머 치매 치료 및 예방용 조성물
WO2013173652A1 (en) 2012-05-16 2013-11-21 Rana Therapeutics, Inc. Compositions and methods for modulating gene expression
EP3842514A1 (en) 2014-09-12 2021-06-30 Whitehead Institute for Biomedical Research Cells expressing apolipoprotein e and uses thereof
KR20160121450A (ko) 2015-04-10 2016-10-19 경북대학교병원 콜레스테롤 축적에 의한 질환 진단용 마커 조성물 및 이의 이용
KR102825946B1 (ko) * 2016-02-02 2025-06-27 올릭스 주식회사 IL4Rα, TRPA1, 또는 F2RL1을 표적화하는 RNA 복합체를 사용한 아토피 피부염 및 천식의 치료
EP4081302A4 (en) * 2019-12-23 2025-01-29 University Of Massachusetts OLIGONUCLEOTIDES FOR TISSUE-SPECIFIC GENE EXPRESSION MODULATION

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2213738A2 (en) * 2002-11-14 2010-08-04 Dharmacon, Inc. siRNA molecules targeting Bcl-2
US20060257851A1 (en) * 2002-11-26 2006-11-16 Itzhak Bentwich Bioinformatically detectable group of novel viral regulatory genes and uses thereof
US20080293655A1 (en) * 2006-02-08 2008-11-27 Huseyin Aygun Novel tandem siRNAS
US20150141320A1 (en) * 2012-05-16 2015-05-21 Rana Therapeutics, Inc. Compositions and methods for modulating gene expression
WO2013181618A2 (en) * 2012-05-31 2013-12-05 The Trustees Of Columbia University In The City Of New York Methods to treat alzheimer's disease using apoe inhibitors
US20170334977A1 (en) * 2014-10-20 2017-11-23 The Brigham And Women's Hospital, Inc. Targeting Apolipoprotein E (APOE) in Neurologic Disease
WO2017132669A1 (en) * 2016-01-31 2017-08-03 University Of Massachusetts Branched oligonucleotides
US20170312367A1 (en) * 2016-01-31 2017-11-02 University Of Massachusetts Branched oligonucleotides

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118460654A (zh) * 2024-07-10 2024-08-09 凯莱英医药集团（天津）股份有限公司 一种Givosiran的制备方法
WO2026057066A1 (zh) * 2024-09-14 2026-03-19 瑞典瑞博科尔制药公司 寡核苷酸、寡核苷酸缀合物及组合物和用途

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CA3133241A1 (en) 2020-09-24
JP2025156319A (ja) 2025-10-14
US20200362341A1 (en) 2020-11-19
JP2022525208A (ja) 2022-05-11
JP7687685B2 (ja) 2025-06-03
WO2020190768A1 (en) 2020-09-24
EP3937951A1 (en) 2022-01-19
EP3937951A4 (en) 2023-04-05

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