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1. 发明申请

WO2006050257A2 DETECTION OF ION CHANNEL OR RECEPTOR ACTIVITY 审中-公开
标题翻译：检测离子通道或受体活性
公开(公告)号：WO2006050257A2
公开(公告)日：2006-05-11
申请号：PCT/US2005/039260
申请日：2005-10-31
申请人： MASSACHUSETTS INSTITUTE OF TECCHNOLOGY , CHILDREN'S MEDICAL CENTER CORPORATION , HOWARD HUGHES MEDICAL INSTITUTE , MARINI, Davide, M. , DESAI, Bimal , DELLING, Markus , SOLIS, Daniel, J. , BELCHER, Angela, M. , CLAPHAM, David, E. , FEBVAY, Sebastien , CARTER, Brett
发明人： MARINI, Davide, M. , DESAI, Bimal , DELLING, Markus , SOLIS, Daniel, J. , BELCHER, Angela, M. , CLAPHAM, David, E. , FEBVAY, Sebastien , CARTER, Brett
IPC分类号： G01N33/53
CPC分类号： C12Q1/005 , B82Y5/00 , B82Y10/00 , G01N21/554 , G01N33/542 , G01N33/54373 , G01N33/6872 , G01N2333/726
摘要： The invention provides nanosensors and nanosensor components for the detection of ion channel activity, receptor activity, or protein protein interactions. Certain of the nanosensor components comprise a nanoparticle and recognition domain. Following contact with cells and, optionally, internalization of the nanosensor component by a cell, the recognition domain binds to a target domain, e.g., a heterologous target domain, of a polypeptide of interest such as an ion channel subunit, G protein coupled receptor (GPCR), or G protein subunit. Ion channel activity, GPCR activity, or altered protein interaction results in a detectable signal. The nanoparticles may be functionalized so that they respond to the presence of an ion by altering their proximity. Certain of the nanosensors utilize the phenomenon of plasmon resonance to produce a signal while others utilize magnetic properties, RET, and/or ion-sensitive moieties. Also provided are polypeptides, e.g., ion channel subunits, comprising a heterologous target domain, and cell lines that express the polypeptides. Further provided are a variety of methods for detecting ion channel activity, receptor activity, or protein interaction and for identifying compounds that modulate one or more of these. In certain embodiments the invention allows the user to detect the activity of specific ion channels even in the presence of other channels that permit passage of the same ion(s) or result in activation of the same downstream targets, thereby achieving improved specificity in high throughput screens while at the same time providing a high signal to noise ratio.
摘要翻译：本发明提供用于检测离子通道活性，受体活性或蛋白质蛋白相互作用的纳米传感器和纳米传感器组分。某些纳米传感器组件包含纳米颗粒和识别结构域。在与细胞接触并且任选地，通过细胞使纳米传感器组分内化后，识别结构域结合感兴趣的多肽的靶结构域例如异源靶结构域，例如离子通道亚基，G蛋白偶联受体（ GPCR）或G蛋白亚基。离子通道活性，GPCR活性或改变的蛋白质相互作用导致可检测的信号。纳米颗粒可以被官能化，使得它们通过改变它们的接近度来响应离子的存在。某些纳米传感器利用等离子体共振现象来产生信号，而另一些利用磁性，RET和/或离子敏感部分。还提供了多肽，例如包含异源靶域的离子通道亚单位，以及表达多肽的细胞系。进一步提供了用于检测离子通道活性，受体活性或蛋白质相互作用以及鉴定调节这些中的一种或多种的化合物的各种方法。在某些实施方案中，本发明允许用户即使在允许相同离子通过或导致相同下游靶的活化的其它通道的存在下也检测特定离子通道的活性，从而实现高通量的改善的特异性屏幕同时提供高信噪比。

2. 发明申请

WO2011133925A3 TARGETED AND LIGHT-ACTIVATED CYTOSOLIC DRUG DELIVERY 审中-公开
标题翻译：靶向和活化的CYPOSOLIC药物递送
公开(公告)号：WO2011133925A3
公开(公告)日：2012-03-22
申请号：PCT/US2011033655
申请日：2011-04-22
申请人： MASSACHUSETTS INST TECHNOLOGY , CHILDRENS HOSPITAL BOSTON , FEBVAY SEBASTIEN , MARINI DAVIDE MAURIZIO , CLAPHAM DAVID E
发明人： FEBVAY SEBASTIEN , MARINI DAVIDE MAURIZIO , CLAPHAM DAVID E
IPC分类号： A61K9/14 , A61K9/16 , A61K39/395 , A61K47/02 , A61K47/48 , A61K49/00 , A61P35/00
CPC分类号： A61K47/48015 , A61K9/143 , A61K41/0038 , A61K41/0057 , A61K47/52 , A61K47/6923 , C07K16/28 , C07K2317/77
摘要： The present invention provides methods and compositions for highly precise spatial and temporal control over cytosolic delivery of compounds, in particular, those compounds that would otherwise be cell-impermeable. Among other things, the present invention provides a composition for targeted drug delivery comprising a nanoparticle, a targeting moiety specific for a cell type of interest, a light-activated drug delivery system, wherein the nanoparticles are associated with the targeting moiety and the light-activated drug delivery system.
摘要翻译：本发明提供了用于对化合物，特别是否则将是细胞不可渗透的那些化合物的细胞质递送的高度精确的空间和时间控制的方法和组合物。除其他之外，本发明提供了用于靶向药物递送的组合物，其包含纳米颗粒，特定于感兴趣细胞类型的靶向部分，光活化药物递送系统，其中所述纳米颗粒与靶向部分相关联，活化药物输送系统。

3. 发明申请

WO2011133925A2 TARGETED AND LIGHT-ACTIVATED CYTOSOLIC DRUG DELIVERY 审中-公开
标题翻译：靶向和活化的CYPOSOLIC药物递送
公开(公告)号：WO2011133925A2
公开(公告)日：2011-10-27
申请号：PCT/US2011/033655
申请日：2011-04-22
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , CHILDREN'S HOSPITAL BOSTON , FEBVAY, Sebastien , MARINI, Davide, Maurizio , CLAPHAM, David, E.
发明人： FEBVAY, Sebastien , MARINI, Davide, Maurizio , CLAPHAM, David, E.
IPC分类号： A61K9/14 , A61K9/16 , A61K47/02 , A61K47/48 , A61K39/395 , A61K49/00 , A61P35/00
CPC分类号： A61K47/48015 , A61K9/143 , A61K41/0038 , A61K41/0057 , A61K47/52 , A61K47/6923 , C07K16/28 , C07K2317/77
摘要： The present invention provides methods and compositions for highly precise spatial and temporal control over cytosolic delivery of compounds, in particular, those compounds that would otherwise be cell-impermeable. Among other things, the present invention provides a composition for targeted drug delivery comprising a nanoparticle, a targeting moiety specific for a cell type of interest, a light-activated drug delivery system, wherein the nanoparticles are associated with the targeting moiety and the light-activated drug delivery system.
摘要翻译：本发明提供了用于对化合物，特别是否则将是细胞不可渗透的那些化合物的细胞质递送的高度精确的空间和时间控制的方法和组合物。除其他之外，本发明提供了用于靶向药物递送的组合物，其包含纳米颗粒，特异于感兴趣的细胞类型的靶向部分，光活化药物递送系统，其中所述纳米颗粒与靶向部分相关联，活化药物输送系统。

4. 发明申请

WO2006050257A3 DETECTION OF ION CHANNEL OR RECEPTOR ACTIVITY 审中-公开
标题翻译：检测离子通道或受体活性
公开(公告)号：WO2006050257A3
公开(公告)日：2009-05-07
申请号：PCT/US2005039260
申请日：2005-10-31
申请人： MASSACHUSETTS INST OF TECCHNOL , CHILDRENS MEDICAL CENTER , MARINI DAVIDE M , DESAI BIMAL , DELLING MARKUS , SOLIS DANIEL J , BELCHER ANGELA M , CLAPHAM DAVID E , FEBVAY SEBASTIEN , CARTER BRETT
发明人： MARINI DAVIDE M , DESAI BIMAL , DELLING MARKUS , SOLIS DANIEL J , BELCHER ANGELA M , CLAPHAM DAVID E , FEBVAY SEBASTIEN , CARTER BRETT
IPC分类号： G01N33/551
CPC分类号： C12Q1/005 , B82Y5/00 , B82Y10/00 , G01N21/554 , G01N33/542 , G01N33/54373 , G01N33/6872 , G01N2333/726
摘要： The invention provides nanosensors and nanosensor components for the detection of ion channel activity, receptor activity, or protein protein interactions. Certain of the nanosensor components comprise a nanoparticle and recognition domain. Following contact with cells and, optionally, internalization of the nanosensor component by a cell, the recognition domain binds to a target domain, e.g., a heterologous target domain, of a polypeptide of interest such as an ion channel subunit, G protein coupled receptor (GPCR), or G protein subunit. Ion channel activity, GPCR activity, or altered protein interaction results in a detectable signal. The nanoparticles may be functionalized so that they respond to the presence of an ion by altering their proximity. Certain of the nanosensors utilize the phenomenon of plasmon resonance to produce a signal while others utilize magnetic properties, RET, and/or ion-sensitive moieties. Also provided are polypeptides, e.g., ion channel subunits, comprising a heterologous target domain, and cell lines that express the polypeptides. Further provided are a variety of methods for detecting ion channel activity, receptor activity, or protein interaction and for identifying compounds that modulate one or more of these. In certain embodiments the invention allows the user to detect the activity of specific ion channels even in the presence of other channels that permit passage of the same ion(s) or result in activation of the same downstream targets, thereby achieving improved specificity in high throughput screens while at the same time providing a high signal to noise ratio.
摘要翻译：本发明提供用于检测离子通道活性，受体活性或蛋白质蛋白相互作用的纳米传感器和纳米传感器组分。某些纳米传感器组件包含纳米颗粒和识别结构域。在与细胞接触并且任选地，通过细胞使纳米传感器组分内化后，识别结构域结合感兴趣的多肽的靶结构域例如异源靶结构域，例如离子通道亚基，G蛋白偶联受体（ GPCR）或G蛋白亚基。离子通道活性，GPCR活性或改变的蛋白质相互作用导致可检测的信号。纳米颗粒可以被官能化，使得它们通过改变它们的接近度来响应离子的存在。某些纳米传感器利用等离子体共振现象来产生信号，而另一些利用磁性，RET和/或离子敏感部分。还提供了多肽，例如包含异源靶域的离子通道亚单位，以及表达多肽的细胞系。进一步提供了用于检测离子通道活性，受体活性或蛋白质相互作用以及鉴定调节这些中的一种或多种的化合物的各种方法。在某些实施方案中，本发明允许用户即使在允许相同离子通过或导致相同下游靶的活化的其它通道的存在下也检测特定离子通道的活性，从而实现高通量的改善的特异性屏幕同时提供高信噪比。

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