KR20180093967A - 유전자 교정된 자가유래 각질세포를 사용한 열성 이영양성 수포성 표피박리증의 유전자 치료법 - Google Patents
유전자 교정된 자가유래 각질세포를 사용한 열성 이영양성 수포성 표피박리증의 유전자 치료법 Download PDFInfo
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| IT201700104587A1 (it) * | 2017-09-19 | 2019-03-19 | Holostem Terapie Avanzate S R L | Usi terapeutici di lembi di cellule geneticamente modificate |
| EP3733210A4 (en) * | 2017-12-29 | 2021-10-06 | Genemedicine Co., Ltd. | CELL SHEET FOR GENE DELIVERY |
| RU2730661C2 (ru) * | 2018-12-27 | 2020-08-24 | Селл энд Джин Терапи Лтд | Генотерапевтический ДНК-вектор на основе генотерапевтического ДНК-вектора VTvaf17, несущий целевой ген, выбранный из группы генов COL1A1, COL1A2, P4HA1, P4HA2, COL7A1, CLCA2, ELN, PLOD1 для повышения уровня экспрессии этих целевых генов, способ его получения и применения, штамм Escherichia coli SCS110-AF/VTvaf17-COL1A1, или Escherichia coli SCS110-AF/VTvaf17-COL1A2, или Escherichia coli SCS110-AF/VTvaf17-P4HA1, или Escherichia coli SCS110-AF/VTvaf17-P4HA2, или Escherichia coli SCS110-AF/VTvaf17-COL7A1, или Escherichia coli SCS110-AF/VTvaf17-CLCA2, или Escherichia coli SCS110-AF/VTvaf17-ELN, или Escherichia coli SCS110-AF/VTvaf17- PLOD1, несущий генотерапевтический ДНК-вектор, способ его получения, способ производства в промышленных масштабах генотерапевтического ДНК-вектора |
| WO2020149395A1 (ja) | 2019-01-18 | 2020-07-23 | 国立大学法人大阪大学 | 栄養障害型表皮水疱症治療薬 |
| CN116529361B (zh) * | 2019-10-18 | 2024-01-26 | 北赛泓升(北京)生物科技有限公司 | 使用多顺反子sox2、klf4和任选的c-myc产生诱导多能干细胞 |
| KR20230043906A (ko) * | 2020-07-22 | 2023-03-31 | 고꾸리쯔 다이가꾸 호우징 오사까 다이가꾸 | 영양 장애형 표피 수포증의 치료약 |
| MX2024004434A (es) | 2021-10-12 | 2024-07-09 | Phoenix Tissue Repair Inc | Terapia de reemplazo de proteínas con colágeno 7. |
| JP2025094280A (ja) * | 2022-01-21 | 2025-06-25 | 国立大学法人大阪大学 | 細胞シート |
Family Cites Families (12)
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|---|---|---|---|---|
| US5830725A (en) * | 1995-04-28 | 1998-11-03 | The Board Of Trustees For The Leland Stanford Junior University | Rapid, stable high-titre production of recombing retrovirus |
| US20020090725A1 (en) | 2000-11-17 | 2002-07-11 | Simpson David G. | Electroprocessed collagen |
| NZ516897A (en) * | 1999-07-02 | 2004-01-30 | Human Genome Sciences Inc | Polynucleotides and associated polypeptides for KGF-2 (also known as Fibroblast Growth Factor 12) to promote and accelerate internal and external wound healing |
| FR2857671B1 (fr) * | 2003-07-18 | 2007-10-05 | Centre Nat Rech Scient | Nouveau procede de culture de keratinocytes et ses applications |
| CN1916166B (zh) * | 2006-09-08 | 2010-08-11 | 北京赛尔泰和生物医药科技有限公司 | 自体角膜上皮的制备方法 |
| US8865199B2 (en) * | 2008-11-17 | 2014-10-21 | Ingeneron, Inc. | Biomatrix composition and methods of biomatrix seeding |
| GB201202561D0 (en) * | 2012-02-15 | 2012-03-28 | Univ Dundee | Treatment of skin disorders |
| EP3995158A1 (en) * | 2012-11-06 | 2022-05-11 | Imbed Biosciences, Inc. | Methods and compositions for wound healing |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| CN105087565A (zh) * | 2015-08-21 | 2015-11-25 | 内蒙古自治区人民医院 | 一种营养不良型大疱性表皮松解症核苷酸及其应用 |
| DK3400287T3 (da) * | 2016-01-04 | 2021-03-01 | Univ Leland Stanford Junior | Genterapi for recessiv dystrofisk epidermolysis bullosa under anvendelse af genetisk korrigerede autologe keratinocytter |
| CA3017757A1 (en) * | 2016-03-18 | 2017-09-21 | Intrexon Corporation | Compositions and methods for treatment of type vii collagen deficiencies |
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