CN114746550A - 用于调节剪接和蛋白质表达的组合物和方法 - Google Patents

用于调节剪接和蛋白质表达的组合物和方法 Download PDF

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CN114746550A
CN114746550A CN202080073358.0A CN202080073358A CN114746550A CN 114746550 A CN114746550 A CN 114746550A CN 202080073358 A CN202080073358 A CN 202080073358A CN 114746550 A CN114746550 A CN 114746550A
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premrna
mrna
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伊莎贝尔·阿兹纳雷兹
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Stoke Therapeutics Inc
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CN202080073358.0A 2019-08-19 2020-08-19 用于调节剪接和蛋白质表达的组合物和方法 Pending CN114746550A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201962888887P 2019-08-19 2019-08-19
US62/888,887 2019-08-19
US202063049262P 2020-07-08 2020-07-08
US63/049,262 2020-07-08
PCT/US2020/047081 WO2021034985A1 (en) 2019-08-19 2020-08-19 Compositions and methods for modulating splicing and protein expression

Publications (1)

Publication Number Publication Date
CN114746550A true CN114746550A (zh) 2022-07-12

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US (1) US20220290142A1 (enExample)
EP (1) EP4017979A4 (enExample)
JP (1) JP2022544702A (enExample)
KR (1) KR20220104677A (enExample)
CN (1) CN114746550A (enExample)
AU (1) AU2020334067A1 (enExample)
BR (1) BR112022002905A2 (enExample)
CA (1) CA3147970A1 (enExample)
IL (1) IL290595A (enExample)
MX (1) MX2022002198A (enExample)
WO (1) WO2021034985A1 (enExample)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7652713B2 (ja) * 2019-05-27 2025-03-27 ビジョン ファーマ ピーティーワイ リミテッド 新規の網膜色素変性処置
KR20220054401A (ko) * 2019-09-03 2022-05-02 더 리전츠 오브 더 유니버시티 오브 콜로라도, 어 바디 코퍼레이트 감염의 숙주 rna 바이오마커의 신속한 조기-검출 및 인간의 covid-19 코로나바이러스 감염의 조기 식별을 위한 시스템, 방법 및 조성물
CN115916977A (zh) * 2020-05-11 2023-04-04 弗洛里神经科学与心理健康研究所 用于治疗与syngap1中功能失去突变相关的障碍的组合物和方法
CN117980479A (zh) * 2021-06-21 2024-05-03 斯托克制药公司 用于治疗基于无义介导的rna衰变的病状和疾病的反义寡聚体
WO2023004021A2 (en) * 2021-07-23 2023-01-26 The Children's Medical Center Corporation Zinc finger ccch-type containing 14 (zc3h14) mutants and methods of use
WO2023163801A1 (en) * 2022-02-24 2023-08-31 Q-State Biosciences, Inc. Therapeutics for syngap haploinsufficiency
EP4504951A2 (en) * 2022-04-05 2025-02-12 The Johns Hopkins University Methods and materials for treating syngap1-associated neurodevelopmental disorders
WO2023212625A1 (en) * 2022-04-28 2023-11-02 AcuraStem Incorporated Syf2 antisense oligonucleotides
US20250313832A1 (en) * 2022-05-13 2025-10-09 The Trustees Of The University Of Pennsylvania Compositions for treating syngap-1 related neurodevelopmental disorders
US20250368991A1 (en) * 2022-06-28 2025-12-04 Agency For Science, Technology And Research Oligonucleotides
WO2025090633A1 (en) * 2023-10-23 2025-05-01 Regeneron Pharmaceuticals, Inc. Compositions and methods comprising small nuclear rna (snrna) for treating genetic epilepsies
WO2025111249A2 (en) * 2023-11-20 2025-05-30 Dana-Farber Cancer Institute, Inc. Methods, kits and systems for determining sarcomatoid differentiation of renal cell carcinoma and methods for treating based on the same
GB202401412D0 (en) * 2024-02-02 2024-03-20 Harness Therapeutics Ltd Functional nucleic acid

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010051632A1 (en) * 2008-11-07 2010-05-14 Centre Hospitalier Universitaire Sainte-Justine Syngap1 dysfunctions and uses thereof in diagnostic and therapeutic applications for mental retardation
WO2016054615A2 (en) * 2014-10-03 2016-04-07 Cold Spring Harbor Laboratory Targeted augmentation of nuclear gene output
CN109312343A (zh) * 2015-12-14 2019-02-05 冷泉港实验室 用于治疗常染色体显性精神发育迟滞5型和Dravet综合征的反义寡聚体

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009064920A2 (en) * 2007-11-13 2009-05-22 Isis Pharmaceuticals, Inc. Compounds and methods for modulating protein expression
CN108603230A (zh) * 2015-10-09 2018-09-28 南安普敦大学 基因表达的调节与蛋白质表达失调的筛选
EP3390666A4 (en) * 2015-12-14 2019-08-07 Cold Spring Harbor Laboratory COMPOSITIONS AND METHODS OF TREATING NURSE DISEASES
EP3390635A4 (en) * 2015-12-14 2019-05-01 Cold Spring Harbor Laboratory Antisense oligomers for the treatment of a tuberous sclerosis complex
JP2019500345A (ja) * 2015-12-14 2019-01-10 コールド スプリング ハーバー ラボラトリー 肝臓病の処置のための組成物および方法
JP2018538287A (ja) * 2015-12-14 2018-12-27 コールド スプリング ハーバー ラボラトリー 多発性嚢胞腎の処置のためのアンチセンスオリゴマー
JP7036723B2 (ja) * 2015-12-14 2022-03-15 コールド スプリング ハーバー ラボラトリー 眼疾患の処置のための組成物および方法
EA201991309A1 (ru) * 2016-11-28 2019-11-29 Способы модуляции сплайсинга рнк
KR102318434B1 (ko) * 2017-08-25 2021-11-01 스톡 테라퓨틱스, 인크. 병태 및 질환 치료용 안티센스 올리고머
HUE070436T2 (hu) * 2017-10-23 2025-06-28 Stoke Therapeutics Inc Antiszensz oligomerek nonszensz-mediált RNS-lebomláson alapuló állapotok és betegségek kezelésére

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010051632A1 (en) * 2008-11-07 2010-05-14 Centre Hospitalier Universitaire Sainte-Justine Syngap1 dysfunctions and uses thereof in diagnostic and therapeutic applications for mental retardation
WO2016054615A2 (en) * 2014-10-03 2016-04-07 Cold Spring Harbor Laboratory Targeted augmentation of nuclear gene output
CN109312343A (zh) * 2015-12-14 2019-02-05 冷泉港实验室 用于治疗常染色体显性精神发育迟滞5型和Dravet综合征的反义寡聚体

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KR20220104677A (ko) 2022-07-26
IL290595A (en) 2022-04-01
MX2022002198A (es) 2022-05-24
US20220290142A1 (en) 2022-09-15
BR112022002905A2 (pt) 2022-07-12
JP2022544702A (ja) 2022-10-20
EP4017979A4 (en) 2024-03-27
AU2020334067A1 (en) 2022-03-17
CA3147970A1 (en) 2021-02-25
EP4017979A1 (en) 2022-06-29
WO2021034985A1 (en) 2021-02-25

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