KR20100061792A - 안 질환을 치료 또는 예방하기 위한 간섭 ｒｎａ 분자의 자기-상보적 ａａｖ 매개 전달 - Google Patents
안 질환을 치료 또는 예방하기 위한 간섭 ｒｎａ 분자의 자기-상보적 ａａｖ 매개 전달 Download PDFInfo
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- KR20100061792A KR20100061792A KR1020107003620A KR20107003620A KR20100061792A KR 20100061792 A KR20100061792 A KR 20100061792A KR 1020107003620 A KR1020107003620 A KR 1020107003620A KR 20107003620 A KR20107003620 A KR 20107003620A KR 20100061792 A KR20100061792 A KR 20100061792A
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- interfering rna
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| EP2019143A1 (en) | 2007-07-23 | 2009-01-28 | Genethon | CNS gene delivery using peripheral administration of AAV vectors |
| EP2058401A1 (en) | 2007-10-05 | 2009-05-13 | Genethon | Widespread gene delivery to motor neurons using peripheral injection of AAV vectors |
| EP2287323A1 (en) | 2009-07-31 | 2011-02-23 | Association Institut de Myologie | Widespread gene delivery to the retina using systemic administration of AAV vectors |
| CN105821079B (zh) * | 2010-04-23 | 2021-10-26 | 佛罗里达大学研究基金公司 | 用于治疗莱伯氏先天性黑蒙-1(lca1)的raav-鸟苷酸环化酶组合物及方法 |
| CN103505743A (zh) | 2012-06-21 | 2014-01-15 | 北京命码生科科技有限公司 | 含功能性microRNA/siRNA的细胞微粒子及其应用 |
| EP4012035B1 (en) * | 2014-09-16 | 2024-11-06 | Genzyme Corporation | Adeno-associated viral vectors for treating myocilin (myoc) glaucoma |
| SG10201913430VA (en) * | 2014-09-16 | 2020-03-30 | Genzyme Corp | Adeno-associated viral vectors for treating myocilin (myoc) glaucoma |
| PL4012035T3 (pl) * | 2014-09-16 | 2025-03-24 | Genzyme Corporation | Wektory wirusowe związane z adenowirusami do leczenia jaskry miocylinowej (myoc) |
| GB201809588D0 (en) * | 2018-06-12 | 2018-07-25 | Univ Bristol | Materials and methods for modulating intraocular and intracranial pressure |
| KR20220076510A (ko) | 2019-10-08 | 2022-06-08 | 트러스티스 오브 보스톤 칼리지 | 다수의 서로 다른 비천연 아미노산을 함유하는 단백질 및 이러한 단백질의 제조 및 사용 방법 |
| JP2023517011A (ja) | 2020-03-05 | 2023-04-21 | ネオティーエックス セラピューティクス リミテッド | 免疫細胞を用いて癌を治療するための方法および組成物 |
| EP4161583A1 (en) * | 2020-06-05 | 2023-04-12 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods and pharmaceutical compositions for treating ocular diseases |
Family Cites Families (20)
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| US20040198682A1 (en) * | 2001-11-30 | 2004-10-07 | Mcswiggen James | RNA interference mediated inhibition of placental growth factor gene expression using short interfering nucleic acid (siNA) |
| US20050048529A1 (en) * | 2002-02-20 | 2005-03-03 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA) |
| US20040209832A1 (en) * | 2001-11-30 | 2004-10-21 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| NZ545544A (en) * | 2003-08-13 | 2009-04-30 | Univ Illinois | Silencing of TGF-beta receptor type II expression by sirna |
| WO2006042252A2 (en) * | 2004-10-08 | 2006-04-20 | Potentia Pharmeceuticals, Inc. | Viral complement control proteins for eye disorders |
| TWI386225B (zh) * | 2004-12-23 | 2013-02-21 | Alcon Inc | 用於治療眼睛病症的結締組織生長因子（ＣＴＧＦ）ＲＮＡ干擾（ＲＮＡｉ）抑制技術 |
| TWI401316B (zh) * | 2004-12-23 | 2013-07-11 | Alcon Inc | 用於治療青光眼之血清澱粉樣蛋白Ａ的ＲＮＡｉ抑制作用 |
| TW200639253A (en) * | 2005-02-01 | 2006-11-16 | Alcon Inc | RNAi-mediated inhibition of ocular targets |
| AU2006223131A1 (en) * | 2005-03-11 | 2006-09-21 | Alcon, Inc. | RNAi-mediated inhibition of frizzled related protein-1 for treatment of glaucoma |
| GB0521351D0 (en) * | 2005-10-20 | 2005-11-30 | Genomica Sau | Modulation of TRPV expression levels |
| AR057252A1 (es) * | 2005-12-27 | 2007-11-21 | Alcon Mfg Ltd | Inhibicion de rho quinasa mediada por arni para el tratamiento de trastornos oculares |
| TW200731980A (en) * | 2005-12-29 | 2007-09-01 | Alcon Mfg Ltd | RNAi-mediated inhibition of HIF1A for treatment of ocular angiogenesis |
| TW201336514A (zh) * | 2006-04-13 | 2013-09-16 | Alcon Res Ltd | ＲＮＡ干擾（ＲＮＡｉ）所媒介之與脾酪胺酸激酶相關之發炎症狀的抑制作用（二） |
| WO2007127428A2 (en) * | 2006-04-28 | 2007-11-08 | University Of Florida Research Foundation, Inc. | Double-stranded/self-complementary vectors with a truncated cba promoter and methods of gene delivery |
| CA2650416A1 (en) * | 2006-05-19 | 2007-11-29 | Alcon Research, Ltd. | Rnai-mediated inhibition of tumor necrosis factor .alpha.-related conditions |
| BRPI0715821A2 (pt) * | 2006-08-24 | 2013-07-23 | Alcon Res Ltd | inibiÇço de gremlina mediada por rnai para tratamento de condiÇÕes relacionadas À iop |
| EP2137205A2 (en) * | 2007-02-26 | 2009-12-30 | Quark Pharmaceuticals, Inc. | Inhibitors of rtp801 and their use in disease treatment |
| US7973019B1 (en) * | 2007-10-03 | 2011-07-05 | Alcon Research, Ltd. | Transferrin/transferrin receptor-mediated siRNA delivery |
| TW200932274A (en) * | 2007-12-18 | 2009-08-01 | Alcon Res Ltd | Interfering RNA delivery system and uses thereof |
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