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1. 发明授权

US07939327B2 Simultaneous modulation of multiple genes 有权
标题翻译：同时调控多种基因
公开(公告)号：US07939327B2
公开(公告)日：2011-05-10
申请号：US12072871
申请日：2008-02-28
申请人： Jeffrey Miller , Guofu Li , Carl Pabo , Trevor Collingwood
发明人： Jeffrey Miller , Guofu Li , Carl Pabo , Trevor Collingwood
IPC分类号： C12N15/82 , C12N5/14
CPC分类号： C07K14/4702
摘要： Disclosed herein are compositions and methods that regulate expression of two or more endogenous genes.
摘要翻译：本文公开了调节两个或更多个内源基因表达的组合物和方法。

2. 发明授权

US07361635B2 Simultaneous modulation of multiple genes 有权
公开(公告)号：US07361635B2
公开(公告)日：2008-04-22
申请号：US10651761
申请日：2003-08-29
申请人： Jeffrey Miller , Guofu Li , Carl Pabo , Trevor Collingwood
发明人： Jeffrey Miller , Guofu Li , Carl Pabo , Trevor Collingwood
IPC分类号： A61K38/00 , C12P21/06 , C07K14/00 , C07H21/04 , G01N33/53
CPC分类号： C07K14/4702
摘要： Disclosed herein are compositions and methods that regulate expression of two or more endogenous genes.

3. 发明申请

US20080233641A1 Simultaneous modulation of multiple genes 有权
标题翻译：同时调控多种基因
公开(公告)号：US20080233641A1
公开(公告)日：2008-09-25
申请号：US12072871
申请日：2008-02-28
申请人： Jeffrey Miller , Guofu Li , Carl Pabo , Trevor Collingwood
发明人： Jeffrey Miller , Guofu Li , Carl Pabo , Trevor Collingwood
IPC分类号： C12N5/06 , C12N5/04
CPC分类号： C07K14/4702
摘要： Disclosed herein are compositions and methods that regulate expression of two or more endogenous genes.
摘要翻译：本文公开了调节两个或更多个内源基因表达的组合物和方法。

4. 发明申请

US20050064474A1 Methods and compositions for targeted cleavage and recombination 有权
标题翻译：用于靶向切割和重组的方法和组合物
公开(公告)号：US20050064474A1
公开(公告)日：2005-03-24
申请号：US10912932
申请日：2004-08-06
申请人： Fyodor Urnov , Michael Holmes , Jeffrey Miller , Carl Pabo
发明人： Fyodor Urnov , Michael Holmes , Jeffrey Miller , Carl Pabo
IPC分类号： C07K14/435 , C07K14/47 , C07K14/715 , C12N9/14 , C12N9/22 , C12N15/62 , C12P19/34 , C12Q1/68
CPC分类号： A61K35/12 , C07K14/43595 , C07K14/4717 , C07K14/715 , C07K2319/00 , C07K2319/09 , C07K2319/81 , C12N9/14 , C12N9/22 , C12N15/62 , C12N15/85 , C12N2800/80
摘要： Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain and polynucleotides encoding same. Methods for targeted cleavage include introduction of such fusion proteins, or polynucleotides encoding same, into a cell. Methods for targeted recombination additionally include introduction of an exogenous polynucleotide homologous to a genomic region into cells comprising the disclosed fusion proteins.
摘要翻译：本文公开了用于基因组序列的靶向切割，基因组序列的靶向改变以及基因组区域和与该基因组区域同源的外源多核苷酸之间的靶向重组的方法和组合物。组合物包括包含切割结构域（或切割半结构域）和工程化锌指结构域的融合蛋白和编码它们的多核苷酸。用于靶向切割的方法包括将这种融合蛋白或其编码的多核苷酸引入细胞。用于靶向重组的方法另外包括将与基因组区域同源的外源多核苷酸引入包含所公开的融合蛋白的细胞中。

5. 发明申请

US20050064477A1 Methods and compositions for interaction trap assays 有权
标题翻译：相互作用阱测定法的方法和组成
公开(公告)号：US20050064477A1
公开(公告)日：2005-03-24
申请号：US10915233
申请日：2004-08-10
申请人： J. Joung , Jeffrey Miller , Carl Pabo
发明人： J. Joung , Jeffrey Miller , Carl Pabo
IPC分类号： C12N15/10 , C12Q1/68 , G01N33/50
CPC分类号： C12N15/1055 , C12Q1/6897 , G01N33/50 , G01N33/5008 , G01N33/502 , C12Q2565/201
摘要： The present invention provides methods and compositions for interaction trap assays for detecting protein-protein, protein-DNA, or protein-RNA interactions. The methods and compositions of the invention may also be used to identify agents which may agonize or antagonize a protein-protein, protein-DNA, or protein-RNA interactions. In certain embodiments, the interaction trap system of the invention is useful for screening libraries with greater than 107 members. In other embodiments, the interaction trap system of the invention is used in conjunction with flow cytometry. The invention further provides a means for simultaneously screening a target protein or nucleic acid sequence for the ability to interact with two or more test proteins or nucleic acids.
摘要翻译：本发明提供了用于检测蛋白质 - 蛋白质，蛋白质-DNA或蛋白质 - RNA相互作用的相互作用阱测定法的方法和组合物。本发明的方法和组合物还可用于鉴定可能激动或拮抗蛋白质 - 蛋白质，蛋白质-DNA或蛋白质 - RNA相互作用的试剂。在某些实施方案中，本发明的相互作用捕获系统可用于筛选具有大于10 7个成员的文库。在其它实施方案中，本发明的相互作用阱系统结合流式细胞术使用。本发明还提供了用于同时筛选靶蛋白或核酸序列以获得与两种或多种测试蛋白或核酸相互作用的能力的方法。

6. 发明申请

US20070178454A1 Context sensitive paralell optimization of zinc finger dna binding domains 审中-公开
标题翻译：锌指dna结合域的上下文敏感paralell优化
公开(公告)号：US20070178454A1
公开(公告)日：2007-08-02
申请号：US10532258
申请日：2003-10-23
申请人： J. Joung , Carl Pabo
发明人： J. Joung , Carl Pabo
IPC分类号： C40B30/06 , C40B40/08 , C40B40/10
CPC分类号： C12N15/1034
摘要： The present invention relates to methods of identifying multi-finger Zf polypeptides that bind to a sequence of interest. Zf polypeptides identified using the methods described herein can have affinity and specificity for their target sites that is superior to those produced by alternative methods.
摘要翻译：本发明涉及鉴定结合感兴趣序列的多指Zf多肽的方法。使用本文描述的方法鉴定的Zf多肽可以对其靶位点具有优于通过替代方法产生的那些的亲和力和特异性。

7. 发明申请

US20050202498A1 Poly-zinc finger proteins with improved linkers 有权
标题翻译：具有改良接头的聚锌指蛋白
公开(公告)号：US20050202498A1
公开(公告)日：2005-09-15
申请号：US11110594
申请日：2005-04-20
申请人： Jin-Soo Kim , Carl Pabo
发明人： Jin-Soo Kim , Carl Pabo
IPC分类号： C12N15/09 , A61K38/00 , A61K48/00 , C07K14/00 , C07K14/47 , C07K19/00 , C12P21/00 , C12Q1/68 , C07H21/04 , C12N9/22
CPC分类号： C07K14/00 , C07K14/47 , C07K2319/00
摘要： Polynucleotides encoding chimeric proteins, and methods for their production and use are disclosed. The chimeric proteins comprise a flexible linker between two zinc finger DNA-binding domains, wherein the linker contains eight or more amino acids between the second conserved histidine residue of the carboxy-terminal zinc finger of the first domain and the first conserved cysteine residue of the amino-terminal zinc finger of the second domain.
摘要翻译：公开了编码嵌合蛋白的多核苷酸及其生产和使用的方法。嵌合蛋白质包括两个锌指DNA结合结构域之间的柔性接头，其中连接体在第一结构域的羧基末端锌指的第二保守组氨酸残基与第一结构域的第一保守半胱氨酸残基之间含有八个或更多个氨基酸第二结构域的氨基末端锌指。

8. 发明授权

US5804604A Tat-derived transport polypeptides and fusion proteins 失效
标题翻译： Tat衍生的转运多肽和融合蛋白
公开(公告)号：US5804604A
公开(公告)日：1998-09-08
申请号：US450236
申请日：1995-05-25
申请人： Alan Frankel , Carl Pabo , James G. Barsoum , Stephen E. Fawell , R. Blake Pepinsky
发明人： Alan Frankel , Carl Pabo , James G. Barsoum , Stephen E. Fawell , R. Blake Pepinsky
IPC分类号： A61K47/48 , C07K14/16 , C12N15/87 , C07K7/06 , C07K7/08 , C07K14/155 , C07K19/00
CPC分类号： C07K14/005 , A61K47/48238 , C12N15/87 , C07K2319/10 , C07K2319/55 , C07K2319/71 , C07K2319/80 , C12N2740/16322
摘要： This invention relates to delivery of biologically active cargo molecules, such as polypeptides and nucleic acids, into the cytoplasm and nuclei of cells in vitro and in vivo. Intracellular delivery of cargo molecules according to this invention is accomplished by the use of novel transport polypeptides which comprise HIV tat protein or one or more portions thereof, and which are covalently attached to cargo molecules. The transport polypeptides in preferred embodiments of this invention are characterized by the presence of the tat basic region (amino acids 49-57), the absence of the tat cysteine-rich region (amino acids 22-36) and the absence of the tat exon 2-encoded carboxy-terminal domain (amino acids 73-86) of the naturally-occurring tat protein. By virtue of the absence of the cysteine-rich region, the preferred transport polypeptides of this invention solve the potential problems of spurious trans-activation and disulfide aggregation. The reduced size of the preferred transport polypeptides of this invention also minimizes interference with the biological activity of the cargo molecule.
摘要翻译：本发明涉及生物活性物质分子如多肽和核酸在体外和体内递送到细胞的细胞质和细胞核中。根据本发明的货物分子的细胞内递送通过使用包含HIV tat蛋白或其一个或多个部分并且共价连接到货物分子的新型转运多肽来实现。本发明优选实施方案中的转运多肽的特征在于存在tat碱性区（氨基酸49-57），不存在富含半胱氨酸的区域（氨基酸22-36）和不存在tat外显子 2编码的天然存在的tat蛋白的羧基末端结构域（氨基酸73-86）。由于缺乏富含半胱氨酸的区域，本发明优选的转运多肽解决了假反式激活和二硫键聚集的潜在问题。本发明优选的转运多肽的减小的尺寸还使对货物分子的生物活性的干扰最小化。

9. 发明授权

US5674980A Fusion protein comprising tat-derived transport moiety 失效
标题翻译：包含tat衍生转运部分的融合蛋白
公开(公告)号：US5674980A
公开(公告)日：1997-10-07
申请号：US450098
申请日：1995-05-25
申请人： Alan Frankel , Carl Pabo , James G. Barsoum , Stephen E. Fawell , R. Blake Pepinsky
发明人： Alan Frankel , Carl Pabo , James G. Barsoum , Stephen E. Fawell , R. Blake Pepinsky
IPC分类号： A61K38/00 , A61K39/00 , A61K47/48 , A61K49/00 , C07K14/025 , C07K14/16 , C07K14/21 , C07K14/47 , C12N9/08 , C12N9/22 , C12N15/62 , C12N15/87 , C07K19/00 , C07K14/00 , C07K14/005
CPC分类号： C12Y111/01007 , A61K47/48238 , A61K49/00 , C07K14/005 , C07K14/21 , C07K14/47 , C12N15/62 , C12N15/87 , C12N9/0065 , C12N9/22 , A61K2123/00 , A61K38/00 , A61K39/00 , C07K2319/00 , C07K2319/10 , C07K2319/55 , C07K2319/71 , C07K2319/80 , C12N2710/20022 , C12N2740/16322
摘要： This invention relates to delivery of biologically active cargo molecules, such as polypeptides and nucleic acids, into the cytoplasm and nuclei of cells in vitro and in vivo. Intracellular delivery of cargo molecules according to this invention is accomplished by the use of novel transport polypeptides which comprise HIV tat protein or one or more portions thereof, and which are covalently attached to cargo molecules. The transport polypeptides in preferred embodiments of this invention are characterized by the presence of the tat basic region (amino acids 49-57), the absence of the tat cysteine-rich region (amino acids 22-36) and the absence of the tat exon 2-encoded carboxy-terminal domain (amino acids 73-86) of the naturally-occurring tat protein. By virtue of the absence of the cysteine-rich region, the preferred transport polypeptides of this invention solve the potential problems of spurious trans-activation and disulfide aggregation. The reduced size of the preferred transport polypeptides of this invention also minimizes interference with the biological activity of the cargo molecule.
摘要翻译：本发明涉及生物活性物质分子如多肽和核酸在体外和体内递送到细胞的细胞质和细胞核中。根据本发明的货物分子的细胞内递送通过使用包含HIV tat蛋白或其一个或多个部分并且共价连接到货物分子的新型转运多肽来实现。本发明优选实施方案中的转运多肽的特征在于存在tat碱性区（氨基酸49-57），缺少富含半胱氨酸的区域（氨基酸22-36）和不存在tat外显子 2编码的天然存在的tat蛋白的羧基末端结构域（氨基酸73-86）。由于缺乏富含半胱氨酸的区域，本发明优选的转运多肽解决了假反式激活和二硫键聚集的潜在问题。本发明优选的转运多肽的减小的尺寸还使对货物分子的生物活性的干扰最小化。

10. 发明授权

US5670617A Nucleic acid conjugates of tat-derived transport polypeptides 失效
标题翻译： tat衍生的转运多肽的核酸缀合物
公开(公告)号：US5670617A
公开(公告)日：1997-09-23
申请号：US450246
申请日：1995-05-25
申请人： Alan Frankel , Carl Pabo , James G. Barsoum , Stephen E. Fawell , R. Blake Pepinsky
发明人： Alan Frankel , Carl Pabo , James G. Barsoum , Stephen E. Fawell , R. Blake Pepinsky
IPC分类号： A61K38/00 , A61K39/00 , A61K47/48 , A61K49/00 , C07K14/025 , C07K14/16 , C07K14/21 , C07K14/47 , C12N9/08 , C12N9/22 , C12N15/62 , C12N15/87 , C07H21/00 , C07K7/00 , C07K14/00 , C07K14/155
CPC分类号： C12Y111/01007 , A61K47/48238 , A61K49/00 , C07K14/005 , C07K14/21 , C07K14/47 , C12N15/62 , C12N15/87 , C12N9/0065 , C12N9/22 , A61K2123/00 , A61K38/00 , A61K39/00 , C07K2319/00 , C07K2319/10 , C07K2319/55 , C07K2319/71 , C07K2319/80 , C12N2710/20022 , C12N2740/16322
摘要： This invention relates to delivery of biologically active cargo molecules, such as polypeptides and nucleic acids, into the cytoplasm and nuclei of cells in vitro and in vivo. Intracellular delivery of cargo molecules according to this invention is accomplished by the use of novel transport polypeptides which comprise HIV tat protein or one or more portions thereof, and which are covalently attached to cargo molecules. The transport polypeptides in preferred embodiments of this invention are characterized by the presence of the tat basic region (amino acids 49-57), the absence of the tat cysteine-rich region (amino acids 22-36) and the absence of the tat exon 2-encoded carboxy-terminal domain (amino acids 73-86) of the naturally-occurring tat protein. By virtue of the absence of the cysteine-rich region, the preferred transport polypeptides of this invention solve the potential problems of spurious trans-activation and disulfide aggregation. The reduced size of the preferred transport polypeptides of this invention also minimizes interference with the biological activity of the cargo molecule.
摘要翻译：本发明涉及生物活性物质分子如多肽和核酸在体外和体内递送到细胞的细胞质和细胞核中。根据本发明的货物分子的细胞内递送通过使用包含HIV tat蛋白或其一个或多个部分并且共价连接到货物分子的新型转运多肽来实现。本发明优选实施方案中的转运多肽的特征在于存在tat碱性区（氨基酸49-57），不存在富含半胱氨酸的区域（氨基酸22-36）和不存在tat外显子 2编码的天然存在的tat蛋白的羧基末端结构域（氨基酸73-86）。由于缺乏富含半胱氨酸的区域，本发明优选的转运多肽解决了假反式激活和二硫键聚集的潜在问题。本发明优选的转运多肽的减小的尺寸还使对货物分子的生物活性的干扰最小化。

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