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1. 发明申请

US20130011920A1 Methods for Reducing Protein Levels in a Cell 有权
标题翻译：降低细胞中蛋白质水平的方法
公开(公告)号：US20130011920A1
公开(公告)日：2013-01-10
申请号：US13522143
申请日：2011-01-17
申请人： Pengbo Zhou
发明人： Pengbo Zhou
IPC分类号： C12N5/071 , C12N15/85
CPC分类号： A61K31/7052 , A61K38/53 , C07K2319/70 , C12N9/93 , C12N15/111 , C12N2310/11 , C12N2310/14 , C12N2320/31 , A61K2300/00
摘要： The present invention provides a method of reducing levels of at least one target protein in a cell. The cell is contacted with a first agent and a second agent. The first agent reduces synthesis of the target protein, e.g., by reducing levels of the mRNA of the target protein or inhibits translation of the mRNA. The second agent accelerates degradation of the target protein. The first agent may contact the cell before, after or simultaneously with the second agent. The first agent and the second agent may be in separate delivery vehicles, or in a single delivery vehicle. The first agent may be an RNAi (RNA interference) molecule, such as a small interfering RNA (siRNA), a small hairpin RNA (shRNA) or a microRNA (miRNA). The second agent may be a chimeric polypeptide containing a ubiquitin ligase polypeptide and a target protein interacting domain. The ubiquitin ligase polypeptide can be an E3 ubiquitin ligase, including, but not limited to, an SCF polypeptide, a HECT polypeptide and a UBR1 polypeptide. In one embodiment, the SCF polypeptide is an F-box polypeptide.
摘要翻译：本发明提供了降低细胞中至少一种靶蛋白水平的方法。细胞与第一药剂和第二药剂接触。第一种药剂可以减少靶蛋白的合成，例如通过降低靶蛋白的mRNA水平或抑制mRNA的翻译。第二种药物加速靶蛋白的降解。第一药剂可以在第二药剂之前，之后或同时与细胞接触。第一代理和第二代理可以在单独的递送车辆中，或者在单个递送车辆中。第一种试剂可以是RNAi（RNA干扰）分子，例如小干扰RNA（siRNA），小发夹RNA（shRNA）或微小RNA（miRNA）。第二药剂可以是含有泛素连接酶多肽和靶蛋白相互作用结构域的嵌合多肽。泛素连接酶多肽可以是E3泛素连接酶，包括但不限于SCF多肽，HECT多肽和UBR1多肽。在一个实施方案中，SCF多肽是F盒多肽。

2. 发明授权

US09597346B2 Methods for reducing protein levels in a cell 有权
公开(公告)号：US09597346B2
公开(公告)日：2017-03-21
申请号：US13522143
申请日：2011-01-17
申请人： Pengbo Zhou
发明人： Pengbo Zhou
IPC分类号： A61K31/7052 , A61K38/53 , C12N9/00 , C12N15/11
CPC分类号： A61K31/7052 , A61K38/53 , C07K2319/70 , C12N9/93 , C12N15/111 , C12N2310/11 , C12N2310/14 , C12N2320/31 , A61K2300/00
摘要： The present invention provides a method of reducing levels of at least one target protein in a cell. The cell is contacted with a first agent and a second agent. The first agent reduces synthesis of the target protein, e.g., by reducing levels of the mRNA of the target protein or inhibits translation of the mRNA. The second agent accelerates degradation of the target protein. The first agent may contact the cell before, after or simultaneously with the second agent. The first agent and the second agent may be in separate delivery vehicles, or in a single delivery vehicle. The first agent may be an RNAi (RNA interference) molecule, such as a small interfering RNA (siRNA), a small hairpin RNA (shRNA) or a microRNA (miRNA). The second agent may be a chimeric polypeptide containing a ubiquitin ligase polypeptide and a target protein interacting domain. The ubiquitin ligase polypeptide can be an E3 ubiquitin ligase, including, but not limited to, an SCF polypeptide, a HECT polypeptide and a UBR1 polypeptide. In one embodiment, the SCF polypeptide is an F-box polypeptide.

3. 发明授权

US08513181B2 Substances and compositions for enhancing DNA repair and methods of use 有权
标题翻译：用于增强DNA修复的物质和组合物及其使用方法
公开(公告)号：US08513181B2
公开(公告)日：2013-08-20
申请号：US12990373
申请日：2009-04-29
申请人： Pengbo Zhou
发明人： Pengbo Zhou
IPC分类号： A61K31/00 , A61K38/00 , C12N15/113
CPC分类号： C07K14/47 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A61K38/53 , C12N9/93 , C12N15/8509 , C12N2800/30
摘要： The invention provides methods of preventing or treating a condition associated with DNA damage in an animal comprising the administration of a substance that interferes with the activity of the CUL4A ubiquitin ligase. The invention also provides a substance that interferes with the activity of CUL4A, as well as compositions comprising the interfering substance and a carrier. The substance of the invention preferably enhances nucleotide excision repair activity in an animal. The invention further provides methods of identifying substances that negatively or positively modulate the expression and/or activity of CUL4A.
摘要翻译：本发明提供了预防或治疗与动物中DNA损伤相关的病症的方法，包括施用干扰CUL4A泛素连接酶活性的物质。本发明还提供了干扰CUL4A的活性的物质，以及包含干扰物质和载体的组合物。本发明的物质优选增强动物的核苷酸切除修复活性。本发明还提供鉴定负调节或正调节CUL4A的表达和/或活性的物质的方法。

4. 发明申请

US20130236404A2 SUBSTANCES AND COMPOSITIONS FOR ENHANCING DNA REPAIR AND METHODS OF USE 有权
标题翻译：用于增强DNA修复的物质和组合物和使用方法
公开(公告)号：US20130236404A2
公开(公告)日：2013-09-12
申请号：US12990373
申请日：2009-04-29
申请人： Pengbo ZHOU
发明人： Pengbo ZHOU
IPC分类号： A61K8/44 , A61K38/53 , C12Q1/70 , G01N33/573 , A61K38/02 , A61K31/7088 , A61K31/713 , A61K31/715 , A61K31/66 , C07K2/00 , C07H21/00 , C07H21/02 , C08B37/00 , A61K8/46 , A61K8/35 , A61K8/49 , A61K8/29 , A61K8/27 , A61K8/31 , A61Q17/04 , A61P43/00 , A61P35/00 , A61K8/00
CPC分类号： C07K14/47 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A61K38/53 , C12N9/93 , C12N15/8509 , C12N2800/30
摘要： The invention provides methods of preventing or treating a condition associated with DNA damage in an animal comprising the administration of a substance that interferes with the activity of the CUL4A ubiquitin ligase. The invention also provides a substance that interferes with the activity of CUL4A, as well as compositions comprising the interfering substance and a carrier. The substance of the invention preferably enhances nucleotide excision repair activity in an animal. The invention further provides methods of identifying substances that negatively or positively modulate the expression and/or activity of CUL4A.
摘要翻译：本发明提供了预防或治疗与动物中DNA损伤相关的病症的方法，包括施用干扰CUL4A泛素连接酶活性的物质。本发明还提供了干扰CUL4A的活性的物质，以及包含干扰物质和载体的组合物。本发明的物质优选增强动物的核苷酸切除修复活性。本发明还提供鉴定负调节或正调节CUL4A的表达和/或活性的物质的方法。

5. 发明申请

US20110044921A1 SUBSTANCES AND COMPOSITIONS FOR ENHANCING DNA REPAIR AND METHODS OF USE 有权
标题翻译：用于增强DNA修复的物质和组合物及其使用方法
公开(公告)号：US20110044921A1
公开(公告)日：2011-02-24
申请号：US12990373
申请日：2009-04-29
申请人： Pengbo Zhou
发明人： Pengbo Zhou
IPC分类号： A61K8/44 , A61K8/00 , A61K38/53 , C12Q1/70 , G01N33/573 , A61K38/02 , A61K31/7088 , A61K31/713 , A61K31/715 , A61K31/66 , C07K2/00 , C07H21/00 , C07H21/02 , C08B37/00 , A61K8/46 , A61K8/35 , A61K8/49 , A61K8/29 , A61K8/27 , A61K8/31 , A61Q17/04 , A61P43/00 , A61P35/00
CPC分类号： C07K14/47 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A61K38/53 , C12N9/93 , C12N15/8509 , C12N2800/30
摘要： The invention provides methods of preventing or treating a condition associated with DNA damage in an animal comprising the administration of a substance that interferes with the activity of the CUL4A ubiquitin ligase. The invention also provides a substance that interferes with the activity of CUL4A, as well as compositions comprising the interfering substance and a carrier. The substance of the invention preferably enhances nucleotide excision repair activity in an animal. The invention further provides methods of identifying substances that negatively or positively modulate the expression and/or activity of CUL4A.
摘要翻译：本发明提供了预防或治疗与动物中DNA损伤相关的病症的方法，包括施用干扰CUL4A泛素连接酶活性的物质。本发明还提供了干扰CUL4A的活性的物质，以及包含干扰物质和载体的组合物。本发明的物质优选增强动物的核苷酸切除修复活性。本发明还提供鉴定负调节或正调节CUL4A的表达和/或活性的物质的方法。

6. 发明授权

US07223556B1 Targeted proteolysis by recruitment to ubiquitin protein ligases 失效
标题翻译：通过募集到泛素蛋白连接酶的靶向蛋白水解
公开(公告)号：US07223556B1
公开(公告)日：2007-05-29
申请号：US09415795
申请日：1999-10-08
申请人： Pengbo Zhou , Peter M. Howley
发明人： Pengbo Zhou , Peter M. Howley
IPC分类号： C12P21/06 , C12N9/00 , C12N5/16 , C12N5/18 , C12N5/22 , C07H21/04
CPC分类号： C12N15/62 , A61K47/67 , B82Y5/00 , C07K14/005 , C07K14/47 , C07K14/4736 , C07K2319/00 , C07K2319/42 , C07K2319/43 , C07K2319/70 , C07K2319/95 , C12N9/93 , C12N2710/20022
摘要： The present invention relates to methods and reagents for targeting proteolysis of a polypeptide by cis or trans association with a ubiquitin protein ligase, and further provides methods and reagents for inhibiting the ubiquitination and proteolysis of cellular proteins which are recognized by a ubiquitin protein ligase.
摘要翻译：本发明涉及用于通过与泛素蛋白连接酶的顺式或反式结合靶向多肽的蛋白水解的方法和试剂，并且还提供用于抑制泛素蛋白连接酶识别的细胞蛋白的泛素化和蛋白水解的方法和试剂。

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