公开(公告)号：US08685372B2

公开(公告)日：2014-04-01

申请号：US13264512

申请日：2010-04-15

申请人： Roger Y. Tsien ,  Quyen T. Nguyen ,  Michael Whitney

发明人： Roger Y. Tsien ,  Quyen T. Nguyen ,  Michael Whitney

IPC分类号： A61K49/00 ,  G01N33/53 ,  A61P25/00 ,  C07K19/00 ,  C07K17/02 ,  A61K38/18 ,  C07K7/08 ,  C07K17/10

CPC分类号： C12N15/115 ,  A61K38/00 ,  A61K49/0032 ,  A61K49/0054 ,  C07K7/08 ,  C12N2310/16 ,  G01N33/582

摘要： The present invention provides methods for guiding preservation of neurons or nerves during surgery by administering a fluorescently-labeled peptide or aptamer that specifically binds to the neurons or nerves. The invention further provides targeting molecules of fluorescently-labeled peptides or aptamers that specifically bind to neurons or nerves and for compositions thereof.

摘要翻译： 本发明提供了通过施用特异性结合神经元或神经的荧光标记的肽或适体来指导手术期间神经元或神经保护的方法。 本发明还提供了特异性结合神经元或神经的荧光标记肽或适体的靶向分子及其组合物。

公开(公告)号：US20120148499A1

公开(公告)日：2012-06-14

申请号：US13264512

申请日：2010-04-15

申请人： Roger Y. Tsien ,  Quyen T. Nguyen ,  Michael Whitney

发明人： Roger Y. Tsien ,  Quyen T. Nguyen ,  Michael Whitney

IPC分类号： A61K49/00 ,  G01N33/53 ,  A61K38/10 ,  A61P25/00 ,  C07K19/00 ,  C07K17/02 ,  A61K38/18 ,  C07K7/08 ,  C07K17/10

CPC分类号： C12N15/115 ,  A61K38/00 ,  A61K49/0032 ,  A61K49/0054 ,  C07K7/08 ,  C12N2310/16 ,  G01N33/582

摘要： The present invention provides methods for guiding preservation of neurons or nerves during surgery by administering a fluorescently-labeled peptide or aptamer that specifically binds to the neurons or nerves. The invention further provides targeting molecules of fluorescently-labeled peptides or aptamers that specifically bind to neurons or nerves and for compositions thereof.

摘要翻译： 本发明提供了通过施用特异性结合神经元或神经的荧光标记的肽或适体来指导手术期间神经元或神经保护的方法。 本发明还提供了特异性结合神经元或神经的荧光标记肽或适体的靶向分子及其组合物。

公开(公告)号：US20120014873A1

公开(公告)日：2012-01-19

申请号：US13155168

申请日：2011-06-07

申请人： Tao Jiang ,  Emilia S. Olson ,  Michael Whitney ,  Roger Y. Tsien

发明人： Tao Jiang ,  Emilia S. Olson ,  Michael Whitney ,  Roger Y. Tsien

IPC分类号： A61K38/12 ,  C07K14/00 ,  C07K19/00 ,  C12N5/071 ,  A61K51/08 ,  C07K17/00 ,  A61P35/00 ,  C07K4/00 ,  A61K38/16

CPC分类号： C07K7/08 ,  A61K38/00 ,  A61K41/0095 ,  A61K47/64 ,  A61K47/645 ,  A61K47/65 ,  A61K49/0032 ,  A61K49/0043 ,  A61K49/0056 ,  A61K49/085 ,  A61K49/14 ,  A61K49/146 ,  A61K51/088 ,  C07K14/00 ,  C07K14/4728

摘要： A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. X may be cleaved extracellularly or intracellularly. The molecules of the present invention may be linear, cyclic, branched, or have a mixed structure.

摘要翻译： 本发明的肽的一般结构包括A-X-B-C，其中C是货物部分，B部分包括碱性氨基酸，X是可切割的接头序列，A部分包括酸性氨基酸。 完整结构不被细胞所占据; 然而，在X的细胞外裂解时，B-C部分被吸收，将货物运送到靶细胞。 货物可以是例如用于诊断成像的对比剂，化学治疗药物或用于治疗的放射线敏化剂。 X可能在细胞外或细胞内裂解。 本发明的分子可以是直链，环状，支链或具有混合结构。

公开(公告)号：US09651494B2

公开(公告)日：2017-05-16

申请号：US14118836

申请日：2012-05-21

申请人： Evan Walker Miller ,  Roger Y. Tsien

发明人： Evan Walker Miller ,  Roger Y. Tsien

IPC分类号： G01N21/64 ,  G01N33/50 ,  G01N33/542 ,  C09K11/06

CPC分类号： G01N21/6486 ,  C09K11/06 ,  C09K2211/1007 ,  C09K2211/1011 ,  C09K2211/1088 ,  G01N33/5008 ,  G01N33/542 ,  G01N2500/10

摘要： Compounds and methods for determining transmembrane potential, monitoring changes in transmembrane potential, and/or drug screening are provided. In one aspect, compounds of the invention have a structure according to the formula: E-M-A, wherein A is a fluorophore, selected from xanthenes, coumarins, cyanines, bimanes, and difluoroboradizaindacenes, charged at physiological pH; M is a molecular wire; and E is a hydrophobic moiety, wherein A and E are capable of being involved in a photo-induced, intramolecular electron transfer that quenches the fluorescence of A in response to a voltage condition. When in use, compounds of the invention are membrane-impermeant and oriented within the cell membrane such that the charged moiety localizes at the outer leaflet of the lipid bilayer and the hydrophobic moiety and molecular wire associate with the hydrophobic portion of the lipid bilayer. The rate of electron transfer, fluorescence intensity, and quenching are altered in response to changes in transmembrane potential.

公开(公告)号：US08993256B2

公开(公告)日：2015-03-31

申请号：US12443411

申请日：2007-09-28

申请人： Michael Z. Lin ,  Roger Y. Tsien

发明人： Michael Z. Lin ,  Roger Y. Tsien

IPC分类号： C12Q1/02 ,  C12N9/00 ,  C12N9/48 ,  C12N1/20 ,  C12N15/00 ,  C07H21/04 ,  C12Q1/37 ,  G01N33/58

CPC分类号： C12Q1/37 ,  G01N33/582

摘要： The disclosure provides method and compositions for visualizing protein turnover. In particular, the disclosure provides methods and compositions useful for measuring the age of particular proteins or the dynamics of localized protein translation.

摘要翻译： 本公开提供了用于可视化蛋白质周转的方法和组合物。 特别地，本公开提供了可用于测量特定蛋白质的年龄或局部蛋白质翻译的动力学的方法和组合物。

公开(公告)号：US08759492B2

公开(公告)日：2014-06-24

申请号：US13588957

申请日：2012-08-17

申请人： John Yu-luen Lin ,  Roger Y. Tsien

发明人： John Yu-luen Lin ,  Roger Y. Tsien

IPC分类号： A61K36/00 ,  C12P21/08

CPC分类号： C07K19/00 ,  A61K48/005 ,  A61N5/062 ,  C07K14/705 ,  C07K2319/00 ,  C12N15/62 ,  C12N15/85 ,  C12N15/864 ,  C12N2740/15043 ,  C12N2740/15071 ,  C12N2750/14143 ,  C12N2750/14171

摘要： The invention provides engineered red-shifted channelrhodopsin variants. In some embodiments, the channelrhodopsin variants are characterized by improved membrane trafficking, expression, and/or unique spectral and kinetic properties.

摘要翻译： 本发明提供工程化的红移通道视紫红质变体。 在一些实施方案中，通道视紫红质变体的特征在于改进的膜运输，表达和/或独特的光谱和动力学性质。

公开(公告)号：US20140093907A1

公开(公告)日：2014-04-03

申请号：US14118836

申请日：2012-05-21

申请人： Evan Walker Miller ,  Roger Y. Tsien

发明人： Evan Walker Miller ,  Roger Y. Tsien

IPC分类号： G01N21/64

CPC分类号： G01N21/6486 ,  C09K11/06 ,  C09K2211/1007 ,  C09K2211/1011 ,  C09K2211/1088 ,  G01N33/5008 ,  G01N33/542 ,  G01N2500/10

摘要： Compounds and methods for determining transmembrane potential, monitoring changes in transmembrane potential, and/or drug screening are provided. In one aspect, compounds of the invention have a structure according to the formula: E-M-A, wherein A is a fluorophore, selected from xanthenes, eoumarins, cyanines, bimanes, and difluoroboradizaindacenes, charged at physiological pH; M is a molecular wire; and E is a hydrophobic moiety, wherein A and E are capable of being involved in a photo-induced, intramolecular electron transfer that quenches the fluorescence of A in response to a voltage condition. When in use, compounds of the invention are membrane-impermeant and oriented within the cell membrane such that the charged moiety localizes at the outer leaflet of the lipid bilayer and the hydrophobic moiety and molecular wire associate with the hydrophobic portion of the lipid bilayer. The rate of electron transfer, fluorescence intensity, and quenching are altered in response to changes in transmembrane potential.

摘要翻译： 提供了确定跨膜电位的化合物和方法，监测跨膜电位的变化和/或药物筛选。 在一个方面，本发明的化合物具有下式的结构：其中A是荧光团，选自在生理pH下加入的呫吨，香豆素，花青，双马来酰亚胺和二氟硼烷二恶烷; M是分子线; 并且E是疏水部分，其中A和E能够参与光诱导的分子内电子转移，其响应于电压条件淬灭A的荧光。 当使用时，本发明的化合物是膜不渗透的并且在细胞膜内定向，使得带电部分定位在脂质双层的外部小叶上，并且疏水部分和分子线与脂质双层的疏水部分缔合。 响应于跨膜电位的变化，电子转移速率，荧光强度和淬灭速率发生变化。

公开(公告)号：US20110076711A1

公开(公告)日：2011-03-31

申请号：US12861791

申请日：2010-08-23

申请人： Tom KNAPP ,  Gregor Zlokarnik ,  Paul Negulescu ,  Roger Y. Tsien ,  Timothy James Rink

发明人： Tom KNAPP ,  Gregor Zlokarnik ,  Paul Negulescu ,  Roger Y. Tsien ,  Timothy James Rink

IPC分类号： C12Q1/02

CPC分类号： G01N33/582 ,  C12Q1/682 ,  G01N33/5005 ,  G01N33/542 ,  Y10S436/80 ,  Y10S436/809 ,  Y10T436/13 ,  C12Q2563/107 ,  C12Q2527/125

摘要： The present invention provides a method for reducing undesirable light emission from a sample using at least one photon producing agent and at least one photon reducing agent (e.g. dye-based photon reducing agents). The present invention further provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one collisional quencher. The present invention also provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one quencher, such as an electronic quencher. The present invention also provides a system and method of screening test chemicals in fluorescent assays using photon reducing agents. The present invention also provides compositions, pharmaceutical compositions, and kits for practicing these methods.

摘要翻译： 本发明提供一种使用至少一种光子产生剂和至少一种光子还原剂（例如基于染料的光子还原剂）来减少来自样品的不希望的光发射的方法。 本发明进一步提供了用至少一种光子产生剂和至少一种碰撞猝灭剂减少来自样品（例如生物化学或细胞样品）的不希望的光发射的方法。 本发明还提供了用至少一种光子产生剂和至少一种猝灭剂（例如电子猝灭剂）减少来自样品（例如，生物化学或细胞样品）的不希望的光发射的方法。 本发明还提供了使用光子还原剂在荧光测定中筛选测试化学品的系统和方法。 本发明还提供了用于实施这些方法的组合物，药物组合物和试剂盒。

公开(公告)号：US07854898B2

公开(公告)日：2010-12-21

申请号：US12271762

申请日：2008-11-14

申请人： Andrew A. Pham ,  Peter J. Coassin ,  Alec Tate Harootunian ,  Peter N. Pham ,  Harry Stylli ,  Roger Y. Tsien

发明人： Andrew A. Pham ,  Peter J. Coassin ,  Alec Tate Harootunian ,  Peter N. Pham ,  Harry Stylli ,  Roger Y. Tsien

IPC分类号： B01L3/00

CPC分类号： B01L3/5085 ,  B01J2219/00315 ,  B01J2219/00317 ,  B01J2219/00659 ,  B01J2219/00707 ,  B01J2219/0072 ,  B01L3/50855 ,  B01L9/523 ,  B01L2300/0654 ,  B01L2300/0829 ,  C12M23/12 ,  C40B60/14

摘要： The present invention relates to multi-well platforms, lids, caddies and any combination thereof. The multi-well platforms comprise a plurality of wells that can be of any shape and can be arranged in any ornamental pattern. The lid comprises an area corresponding to the well field. The caddy has a footprint approximately that of a standard 96-well microtiter plate. When the multi-well platform is engaged with the caddy, the wells of the well-field of the multi-well platform are preferably not obscured by the caddy when viewed from the bottom of the combination.

摘要翻译： 本发明涉及多孔平台，盖子，球童及其任何组合。 多井平台包括可以是任何形状的多个井，并且可以以任何装饰图案排列。 盖子包括对应于井场的区域。 球罐的尺寸大约是标准96孔微孔板的面积。 当多孔平台与球童接合时，当从组合的底部观察时，多孔平台的井场的井优选地不被球童遮蔽。

公开(公告)号：US20080293068A1

公开(公告)日：2008-11-27

申请号：US12124888

申请日：2008-05-21

申请人： Roger Y. Tsien ,  Lei Wang

发明人： Roger Y. Tsien ,  Lei Wang

IPC分类号： C12Q1/68 ,  C12P21/04 ,  C12Q1/02

CPC分类号： C12P21/02

摘要： Methods using somatic hypermutation (SHM) for producing polypeptide and nucleic acid variants, and nucleic acids encoding such polypeptide variants are disclosed. Such variants may have desired properties. Also disclosed are novel polypeptides, such as improved fluorescent proteins, produced by the novel methods, and nucleic acids, vectors, and host cells comprising such vectors.

摘要翻译： 公开了使用体细胞超突变（SHM）用于产生多肽和核酸变体的方法，以及编码这种多肽变体的核酸。 这样的变体可以具有期望的性质。 还公开了通过新方法产生的新型多肽，例如改良的荧光蛋白，以及包含这种载体的核酸，载体和宿主细胞。