TW201814044A - 多核苷酸、載體、藥物組成物及其等之用途、以及載體獲得方法 - Google Patents
多核苷酸、載體、藥物組成物及其等之用途、以及載體獲得方法 Download PDFInfo
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| TWI841566B (zh) * | 2018-05-30 | 2024-05-11 | 西班牙商艾斯提夫製藥股份有限公司 | 用於治療黏多醣症 iv a 型之腺相關病毒載體 |
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| US9309534B2 (en) | 2010-07-12 | 2016-04-12 | Universidad Autonoma De Barcelona | Gene therapy composition for use in diabetes treatment |
| EP2692868A1 (en) | 2012-08-02 | 2014-02-05 | Universitat Autònoma De Barcelona | Adeno-associated viral (AAV) vectors useful for transducing adipose tissue |
| RU2692251C2 (ru) | 2013-05-15 | 2019-06-24 | Риджентс Оф Зэ Юниверсити Оф Миннесота | Опосредованный аденоассоциированным вирусом перенос генов в центральную нервную систему |
| US10973931B2 (en) | 2014-09-16 | 2021-04-13 | Universitat Autònoma De Barcelona | Adeno-associated viral vectors for the gene therapy of metabolic diseases |
| ES2824457T3 (es) | 2014-12-05 | 2021-05-12 | UNIV AUTòNOMA DE BARCELONA | Vectores virales para el tratamiento de la diabetes |
| ES2900973T3 (es) | 2015-01-07 | 2022-03-21 | UNIV AUTòNOMA DE BARCELONA | Constructo genético de vector individual que comprende genes de insulina y glucoquinasa |
| BR112020021903A2 (pt) | 2018-04-27 | 2021-03-02 | Rocket Pharmaceuticals, Ltd. | terapia genética para degeneração do snc |
| CA3106010A1 (en) * | 2018-07-12 | 2020-01-16 | Rocket Pharmaceuticals, Ltd. | Gene therapy vectors for treatment of danon disease |
| WO2021007473A1 (en) | 2019-07-10 | 2021-01-14 | Masonic Medical Research Institute | Vgll4 with ucp-1 cis-regulatory element and method of use thereof |
| CN111718947B (zh) * | 2020-06-18 | 2022-08-23 | 舒泰神（北京）生物制药股份有限公司 | 用于治疗ⅲa或ⅲb型粘多糖贮积症的腺相关病毒载体及用途 |
| CN116194154A (zh) | 2020-08-07 | 2023-05-30 | 太空飞船七有限责任公司 | 使用aav载体的plakophilin-2(pkp2)基因疗法 |
| CN114480454B (zh) * | 2020-10-27 | 2024-03-29 | 华东理工大学 | 用于治疗粘多糖贮积症ⅱ型的腺相关病毒载体、药物及其应用 |
Family Cites Families (10)
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| US7232670B2 (en) * | 2001-09-28 | 2007-06-19 | St. Jude Children's Research Hospital | Targeting proteins to cells expressing mannose receptors via expression in insect cells |
| US8227212B2 (en) * | 2003-02-11 | 2012-07-24 | Shire Human Genetic Therapies, Inc. | Cell that expresses a sulfatase and a formylglycine generating enzyme |
| EP2394667A1 (en) | 2010-06-10 | 2011-12-14 | Laboratorios Del Dr. Esteve, S.A. | Vectors and sequences for the treatment of diseases |
| CN107982548A (zh) | 2012-02-07 | 2018-05-04 | 全球生物疗法有限公司 | 核酸输送的区室化方法及其组合物和应用 |
| CN105916990B (zh) * | 2013-08-02 | 2020-02-04 | 巴塞罗那自治大学 | 用于转导脂肪组织的腺相关病毒载体 |
| CA2927366A1 (en) * | 2013-10-24 | 2015-04-30 | Uniqure Ip B.V. | Aav-5 pseudotyped vector for gene therapy for neurological diseases |
| GB201322798D0 (en) * | 2013-12-20 | 2014-02-05 | Oxford Biomedica Ltd | Production system |
| MX383227B (es) | 2014-05-14 | 2025-03-13 | UNIV AUTòNOMA DE BARCELONA | Vectores de virus adenoasociados para el tratamiento de trastornos de almacenamiento lisosomico. |
| AU2016219398A1 (en) | 2015-02-10 | 2017-09-28 | Genzyme Corporation | Enhanced delivery of viral particles to the striatum and cortex |
| US9981021B1 (en) * | 2015-04-09 | 2018-05-29 | Kinetiq, Inc. | Subcutaneous therapeutic enzyme formulations, uses, and methods for generating thereof |
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| TWI841566B (zh) * | 2018-05-30 | 2024-05-11 | 西班牙商艾斯提夫製藥股份有限公司 | 用於治療黏多醣症 iv a 型之腺相關病毒載體 |
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