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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| EP2473031A4 (en) * | 2009-09-02 | 2013-12-04 | Univ Chicago | METHOD AND SYSTEMS FOR THE INDUCIBLE ABERMENTATION OF NERVE CELLS |
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| US20140189897A1 (en) | 2011-06-21 | 2014-07-03 | Mayo Foundation For Medical Education And Research | Transgenic animals capable of being induced to delete senescent cells |
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| 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 |
| 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 |
| AU2013204922B2 (en) | 2012-12-20 | 2015-05-14 | Celgene Corporation | Chimeric antigen receptors |
| CN105518018B (zh) | 2013-03-15 | 2020-04-03 | 细胞基因公司 | 修饰的t淋巴细胞 |
| KR20160002848A (ko) | 2013-03-24 | 2016-01-08 | 오이신 바이오테크놀로지스 | 표적 세포 내에서 치료적 단백질의 표적화된 생산을 위한 시스템 및 방법 |
| US12331086B2 (en) * | 2016-11-14 | 2025-06-17 | Toolgen Incorporated | Artificially engineered SC function control system |
| WO2018129563A1 (en) | 2017-01-09 | 2018-07-12 | Oisin Biotechnologies | Fusogenic lipid nanoparticles and methods for manufacturing and use for therapeutic protein production and for treatment |
| JP7592493B2 (ja) | 2018-04-18 | 2024-12-02 | オイシン バイオテクノロジーズ，インク． | 治療用タンパク質の標的細胞に特異的な産生のための、および、標的細胞に関連する疾患、疾病、または障害の処置のための、融合性脂質ナノ粒子、および、融合性脂質ナノ粒子の製造方法と使用方法 |
| 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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| US5175385A (en) * | 1987-09-03 | 1992-12-29 | Ohio University/Edison Animal Biotechnolgy Center | Virus-resistant transgenic mice |
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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 |
| US6472520B2 (en) * | 1997-03-21 | 2002-10-29 | The Trustees Of Columbia University In The City Of New York | Rat PEG-3 promoter |
| US20030110524A1 (en) * | 1997-07-28 | 2003-06-12 | Bradley Michael John Stringer | Transgenic organisms and their uses |
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| US6235872B1 (en) * | 1998-03-12 | 2001-05-22 | The Burnham Institute | Proapoptotic peptides dependence polypeptides and methods of use |
| US7033595B1 (en) * | 1998-08-04 | 2006-04-25 | Purdue Research Foundation | Pseudotyped retroviruses and stable cell lines for their production |
| EP1131470A4 (en) * | 1998-10-28 | 2004-11-10 | Vysis Inc | CELLULAR NETWORKS AND METHODS FOR DETECTION AND USE OF GENETIC DISORDER MARKERS |
| WO2000026343A2 (en) * | 1998-10-30 | 2000-05-11 | Case Western Reserve University | Tissue specific promoters and transgenic animals 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 |
| JP2004500197A (ja) * | 2000-02-08 | 2004-01-08 | コーネル リサーチ ファンデーション インコーポレーテッド | 光ファイバーを通じた蛍光分光用の多光子励起 |
| 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 |
| WO2002019814A2 (en) * | 2000-09-07 | 2002-03-14 | 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 |
| CA2435829A1 (en) * | 2001-01-25 | 2002-08-01 | 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 |
| AU2003219769A1 (en) * | 2002-02-14 | 2003-09-04 | The Procter And Gamble Company | Disposable excreta collector |
| 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 |
| EP1711597B1 (en) * | 2004-01-14 | 2012-03-07 | 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 |
| EP1909562A4 (en) | 2005-06-14 | 2015-04-08 | Univ Chicago | METHOD FOR TREATING MYELIN LOSS STATES |
| CA2690815A1 (en) * | 2007-06-12 | 2008-12-18 | Case Western Reserve University | Targeted cell death |
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