JP6313203B2 - Ａｌｕ−ｒｎａ誘導変性からの細胞の保護及び細胞保護用阻害剤 - Google Patents
Ａｌｕ−ｒｎａ誘導変性からの細胞の保護及び細胞保護用阻害剤 Download PDFInfo
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Families Citing this family (38)
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|---|---|---|---|---|
| US11512326B2 (en) | 2009-05-26 | 2022-11-29 | University Of Florida Research Foundation, Incorporated | Small angiotensin peptide expression system in mammalian cells |
| CN103328633B (zh) | 2010-10-22 | 2018-07-10 | 成均馆大学校产学协力团 | 诱导rna干扰的核酸分子及其用途 |
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| US10125362B2 (en) | 2012-05-22 | 2018-11-13 | Olix Pharmaceuticals, Inc. | RNA-interference-inducing nucleic acid molecule able to penetrate into cells, and use therefor |
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| WO2016022914A1 (en) * | 2014-08-08 | 2016-02-11 | Moderna Therapeutics, Inc. | Compositions and methods for the treatment of ophthalmic diseases and conditions |
| FI4215527T3 (fi) | 2015-02-26 | 2024-12-19 | Univ Kentucky Res Found | Koostumuksia ja menetelmiä verkkokalvon rappeuman hoitamiseksi |
| US11219623B2 (en) | 2015-02-26 | 2022-01-11 | University Of Kentucky Research Foundation | Inflammasome inhibition for the treatment of Parkinson's disease, Alzheimer's disease and multiple sclerosis |
| CN108350046B (zh) | 2015-09-03 | 2022-04-01 | 在本-古里安大学的B．G．内盖夫科技与应用有限公司 | Vdac1衍生肽的类似物 |
| HK1258902A1 (zh) | 2015-11-10 | 2019-11-22 | B. G. Negev Technologies And Applications Ltd., At Ben-Gurion University | 减少癌症干细胞致瘤性的手段和方法 |
| KR102727666B1 (ko) | 2015-11-16 | 2024-11-08 | 올릭스 주식회사 | MyD88 또는 TLR3을 타겟팅하는 RNA 복합체를 이용한 연령-관련 황반 변성의 치료 |
| KR102825946B1 (ko) | 2016-02-02 | 2025-06-27 | 올릭스 주식회사 | IL4Rα, TRPA1, 또는 F2RL1을 표적화하는 RNA 복합체를 사용한 아토피 피부염 및 천식의 치료 |
| WO2017212477A1 (en) * | 2016-06-07 | 2017-12-14 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Backbone cyclized inhibitory peptides of myeloid differentiation factor 88 (myd88) |
| US11130951B2 (en) * | 2016-06-09 | 2021-09-28 | The General Hospital Corporation | Modulating the cellular stress response |
| KR101916652B1 (ko) | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
| WO2018039371A1 (en) * | 2016-08-26 | 2018-03-01 | The Regents Of The University Of California | Compositions and methods for inhibiting stem cell aging |
| JP7213555B2 (ja) | 2016-12-23 | 2023-01-27 | シーエーエスピー－エイド インク． | 神経学的状態の予防および治療のためのカスパーゼ１の阻害およびその使用 |
| KR20190108167A (ko) | 2017-02-10 | 2019-09-23 | 성균관대학교산학협력단 | Rna 간섭을 위한 긴 이중가닥 rna |
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| EP3607063A4 (en) * | 2017-04-03 | 2021-01-13 | Duke University | COMPOSITIONS AND METHODS FOR DIFFERENTIAL INDUCTION OF CELLULAR DEATH AND INTERFERON EXPRESSION |
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| EP3813805A4 (en) * | 2018-06-27 | 2021-08-25 | Children's Medical Center Corporation | COMPOUNDS FOR INHIBITION OF INFLAMMATION |
| KR102138256B1 (ko) * | 2018-09-13 | 2020-08-13 | 한국과학기술연구원 | 케스페이즈-1 활성 측정용 프로브, 이를 포함하는 염증성 질환 진단용 조성물 |
| WO2020076960A1 (en) * | 2018-10-09 | 2020-04-16 | Jayakrishna Ambati | Endogenous cytoplasmic alu complementary dna in age-related macular degeneration |
| CN110305957B (zh) * | 2019-08-22 | 2022-07-29 | 中国水产科学研究院淡水渔业研究中心 | 一种鉴定黄颡鱼脂肪肝程度的试剂盒及其鉴定方法 |
| KR20220066071A (ko) * | 2019-08-23 | 2022-05-23 | 유니버시티 오브 버지니아 페이턴트 파운데이션 | 염증 질환을 표적하는 ddx17 및 nlrc4 |
| CN115484986A (zh) * | 2020-01-06 | 2022-12-16 | 海阳制药 | 用于预防或治疗黄斑变性的含有细胞可渗透的核酸复合物作为活性成分的组合物 |
| EP4103177A4 (en) * | 2020-02-11 | 2024-03-27 | University of Virginia Patent Foundation | COMPOSITIONS AND METHODS FOR THE TREATMENT AND/OR PREVENTION OF EYE DISEASES |
| CN111358950A (zh) * | 2020-03-20 | 2020-07-03 | 厦门大学 | Caspase-1及ASC/Caspase-8作为靶点的应用 |
| US20240011030A1 (en) * | 2020-08-10 | 2024-01-11 | Novartis Ag | Treatments for retinal degenerative diseases |
| JP2023549257A (ja) | 2020-11-18 | 2023-11-22 | ノバルティス アーゲー | Ｎｌｒｃ４－ｇｏｆインフラマソーム病の処置における使用のための二特異性抗体 |
| CN114099683B (zh) * | 2021-12-28 | 2022-12-16 | 首都医科大学附属北京同仁医院 | Nox2特异性抑制剂在制备视网膜变性药物中的应用 |
Family Cites Families (19)
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|---|---|---|---|---|
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| US20030186903A1 (en) * | 2001-11-23 | 2003-10-02 | Isis Pharmaceuticals Inc. | Antisense modulation of MyD88 expression |
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| WO2006006948A2 (en) * | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
| WO2005105133A2 (en) * | 2004-04-23 | 2005-11-10 | Massachusetts Eye And Ear Infirmary | Methods and compositions for preserving the viability of photoreceptor cells |
| US20080064643A1 (en) * | 2004-12-20 | 2008-03-13 | Paolo Carminati | Myd88 Homodimerization Inhibitors |
| US7879992B2 (en) * | 2005-01-31 | 2011-02-01 | Isis Pharmaceuticals, Inc. | Modification of MyD88 splicing using modified oligonucleotides |
| EP1746167A1 (en) * | 2005-07-20 | 2007-01-24 | Apoxis SA | Method for the identification of compounds susceptible to inhibit inflammation |
| WO2007077042A1 (en) * | 2006-01-06 | 2007-07-12 | Topotarget Switzerland Sa | New method for the treatment of gout or pseudogout |
| AU2007329539A1 (en) | 2006-12-01 | 2008-06-12 | George Mason University | Inhibition of brain enzymes involved in cerebral amyloid angiopathy and macular degeneration |
| US20100247538A1 (en) * | 2007-05-29 | 2010-09-30 | Yale University | IL-18 and Protein Kinase R Inhibition for the Treatment of COPD |
| US20090227487A1 (en) * | 2008-03-05 | 2009-09-10 | Jeremy Pearl | Methods for the control of macrophage-associated inflammation |
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