JP2010531638A5 - - Google Patents
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- JP2010531638A5 JP2010531638A5 JP2010512360A JP2010512360A JP2010531638A5 JP 2010531638 A5 JP2010531638 A5 JP 2010531638A5 JP 2010512360 A JP2010512360 A JP 2010512360A JP 2010512360 A JP2010512360 A JP 2010512360A JP 2010531638 A5 JP2010531638 A5 JP 2010531638A5
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| US20120233713A1 (en) * | 2009-09-02 | 2012-09-13 | Brian Popko | Methods and systems for inducible ablation of neural cells |
| US8269827B2 (en) * | 2009-09-29 | 2012-09-18 | General Electric Company | System and methods for mapping fluorescent images into a bright field color space |
| WO2012177927A1 (en) | 2011-06-21 | 2012-12-27 | Mayo Foundation For Medical Education And Research | Transgenic animals capable of being induced to delete senescent cells |
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| US20150064137A1 (en) | 2012-04-17 | 2015-03-05 | Kythera Biopharmaceuticals, Inc. | Use of engineered viruses to specifically kill senescent cells |
| US9901080B2 (en) | 2012-08-23 | 2018-02-27 | Buck Institute For Research On Aging | Transgenic mouse having a transgene that converts a prodrug into a cytotoxic compound in senescent cells |
| US9901081B2 (en) | 2012-08-23 | 2018-02-27 | Buck Institute For Research On Aging | Transgenic mouse for determining the role of senescent cells in cancer |
| AU2013204922B2 (en) | 2012-12-20 | 2015-05-14 | Celgene Corporation | Chimeric antigen receptors |
| JP6493692B2 (ja) * | 2013-03-15 | 2019-04-10 | セルジーン コーポレイション | 修飾されたｔリンパ球 |
| BR112015024605A2 (pt) | 2013-03-24 | 2017-07-18 | Oisin Biotechnologies | sistemas e métodos para a produção visada de proteína terapêutica dentro de célula alvo |
| US12570981B2 (en) * | 2016-03-21 | 2026-03-10 | University Of Virginia Patent Foundation | Genetically modified mouse with conditional deletion of LRP1 in oligodendrocytes |
| KR102437228B1 (ko) * | 2016-11-14 | 2022-08-30 | 주식회사 툴젠 | 인위적으로 조작된 sc 기능 조절 시스템 |
| JP2020503390A (ja) | 2017-01-09 | 2020-01-30 | オイシン バイオテクノロジーズ， インコーポレイテッド | 治療用タンパク質の標的細胞特異的な産生のため、および標的細胞に関連する疾患、状態、または障害の治療のための、膜融合性脂質ナノ粒子、ならびにその作製および使用のための方法 |
| CN112312918A (zh) | 2018-04-18 | 2021-02-02 | 奥依信生物技术公司 | 促融合脂质纳米粒和制备其的方法以及其用于靶细胞特异性产生治疗蛋白和治疗与靶细胞有关的疾病、病况或障碍的用途 |
| CN115197989A (zh) * | 2021-04-09 | 2022-10-18 | 中国科学院分子细胞科学卓越创新中心 | 基于细胞死活表型的药物靶点拮抗剂的新型筛选系统 |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| FR2717824B1 (fr) * | 1994-03-25 | 1996-04-26 | Rhone Poulenc Rorer Sa | Virus recombinants, préparation et utilisation en thérapie génique. |
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| US6143557A (en) * | 1995-06-07 | 2000-11-07 | Life Technologies, Inc. | Recombination cloning using engineered recombination sites |
| US5837837A (en) * | 1997-02-27 | 1998-11-17 | Millennium Pharmaceuticals, Inc. | Nucleic acids molecules encoding Caspase-8h and Caspase-8i |
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| US20030110524A1 (en) * | 1997-07-28 | 2003-06-12 | Bradley Michael John Stringer | Transgenic organisms and their uses |
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| WO2000024940A1 (en) * | 1998-10-28 | 2000-05-04 | Vysis, Inc. | Cellular arrays and methods of detecting and using genetic disorder markers |
| US6313373B1 (en) * | 1998-10-30 | 2001-11-06 | Case Western Reserve University | Tissue specific promoters and transgenic mouse for the screening of pharmaceuticals |
| US7109317B1 (en) * | 1998-11-06 | 2006-09-19 | President And Fellows Of Harvard College | FK506-based regulation of biological events |
| US6903244B1 (en) * | 1999-02-26 | 2005-06-07 | University Of Utah Research Foundation | Mice which are +/− or −/− for the elastin gene as models for vascular disease |
| US6881555B2 (en) * | 1999-03-19 | 2005-04-19 | Aventis Pharmaceuticals Inc. | AKT nucleic acids, polypeptides, and uses thereof |
| US6890726B1 (en) * | 1999-04-06 | 2005-05-10 | Oklahoma Medical Research Foundation | Method for selecting recombinase variants with altered specificity |
| CA2398029A1 (en) * | 2000-02-08 | 2001-08-16 | Cornell Research Foundation, Inc. | Multiphoton excitation through optical fibers for fluorescence spectroscopy |
| US7196182B2 (en) * | 2000-05-24 | 2007-03-27 | The Burnham Institute | Card domain containing polypeptides, encoding nucleic acids, and methods of use |
| WO2002005634A2 (en) * | 2000-07-13 | 2002-01-24 | University Of South Florida | Transgenic animal and methods |
| US6891081B1 (en) * | 2000-08-14 | 2005-05-10 | The Trustees Of Columbia University In The City Of New York | Transgenic mice over-expressing amyloid-beta alcohol dehydrogenase (ABAD) in brain as model of alzheimer's disease and uses thereof |
| US6753456B2 (en) * | 2000-09-07 | 2004-06-22 | California Institute Of Technology | Point mutant mice with hypersensitive alpha 4 nicotinic receptors: dopaminergic pathology and increased anxiety |
| US6967725B2 (en) * | 2000-10-13 | 2005-11-22 | Lucent Technologies Inc. | System and method for optical scanning |
| AU2002239538A1 (en) * | 2000-12-06 | 2002-06-18 | Deltagen, Inc. | Transgenic mice containing glucagon receptor gene disruptions |
| US6656971B2 (en) | 2001-01-25 | 2003-12-02 | Guilford Pharmaceuticals Inc. | Trisubstituted carbocyclic cyclophilin binding compounds and their use |
| US7169564B1 (en) | 2001-06-26 | 2007-01-30 | Anaderm Research Corporation | FKBP51/52 and CyP40-mediated mammalian hair growth |
| CN1292720C (zh) * | 2002-02-14 | 2007-01-03 | 宝洁公司 | 一次性排泄物收集器 |
| US7153685B2 (en) * | 2002-03-11 | 2006-12-26 | The Board Of Trustees Of The University Of Illinois | Tamoxifen and 4-hydroxytamoxifen-activated system for regulated production of proteins in eukaryotic cells |
| US20060030541A1 (en) * | 2002-04-05 | 2006-02-09 | Proskelia | Genes involved in osteogenesis, and methods of use |
| WO2004005531A2 (en) * | 2002-07-05 | 2004-01-15 | Roger Williams Medical Center | Targeting and tracking of cells to specific organs and tissues in vivo |
| US20050143330A1 (en) * | 2002-09-30 | 2005-06-30 | Ron Mandel | Method for the treatment of Parkinson's Disease |
| US7638331B2 (en) | 2004-01-02 | 2009-12-29 | The Administration of the Tulane Rducation Fund | Directed apoptosis in COX-2 overexpressing cancer cells through expression targeted gene delivery |
| CA2553303C (en) * | 2004-01-14 | 2014-06-10 | Novahep Ab | Human hepatic progenitor cells and methods of use thereof |
| WO2006029161A2 (en) * | 2004-09-07 | 2006-03-16 | The Board Of Regents For Oklahoma State University | Cell specific gene silencing using cell-specific promoters in vitro and in vivo |
| WO2006056998A2 (en) | 2004-11-29 | 2006-06-01 | Yeda Research And Development Co. Ltd. | Methods of cell therapy, neurogenesis and oligodendrogenesis |
| EP1710316A1 (en) * | 2005-04-08 | 2006-10-11 | Max-Delbrück-Centrum Für Molekulare Medizin | Reconstructed human mariner transposon capable of stable gene transfer into chromosomes in vertebrates |
| US7423194B2 (en) | 2005-06-14 | 2008-09-09 | University Of Chicago | Animal models for demyelination disorders |
| JP2008546704A (ja) * | 2005-06-14 | 2008-12-25 | ユニバーシティ オブ シカゴ | 脱髄障害を処置するための方法 |
| JP2010531638A (ja) * | 2007-06-12 | 2010-09-30 | ケース ウエスタン リザーブ ユニバーシティ | 標的化された細胞死 |
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