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1. 发明授权

US07407744B2 Cytomegalovirus gene function and methods for developing antivirals, anti-CMV vaccines, and CMV-based vectors 有权
标题翻译：巨细胞病毒基因功能和开发抗病毒药，抗CMV疫苗和基于CMV的载体的方法
公开(公告)号：US07407744B2
公开(公告)日：2008-08-05
申请号：US10897508
申请日：2004-07-23
申请人： Fenyong Liu , Walter Dunn , Cassie Chou
发明人： Fenyong Liu , Walter Dunn , Cassie Chou
IPC分类号： C12Q1/70
CPC分类号： C12N7/00 , C07K14/005 , C12N2710/16122 , C12N2710/16161 , C12Q1/18 , G01N2333/045
摘要： A global functional analysis of HCMV genes is performed by constructing virus gene-deletion mutants and examining their growth phenotypes in different natural HCMV host cells. This systematic analysis of the HCMV genome identified 45 viral ORFs essential for viral replication and characterizes of 115 growth-dispensable viral genes. Of particular interest is the finding that HCMV encodes genes (temperance factors) that repress its own replication on a cell type-specific basis. In addition to HCMV, pathogen temperance may be a strategy employed by other infectious agents to enhance their long-term survivability within their respective host population.
摘要翻译：通过构建病毒基因缺失突变体并检查其在不同天然HCMV宿主细胞中的生长表型来进行HCMV基因的全局功能分析。对HCMV基因组的这种系统分析鉴定了病毒复制所必需的45种病毒ORF，并描述了115种可生长需要的病毒基因。特别感兴趣的是HCMV编码在细胞类型特异性基础上抑制其自身复制的基因（节制因子）的发现。除了HCMV之外，病原体温度可能是其他感染因子在其各自宿主群体中增强其长期存活能力的策略。

2. 发明申请

US20050064394A1 Cytomegalovirus gene function and methods for developing antivirals, anti-CMV vaccines, and CMV-based vectors 有权
标题翻译：巨细胞病毒基因功能和开发抗病毒药，抗CMV疫苗和基于CMV的载体的方法
公开(公告)号：US20050064394A1
公开(公告)日：2005-03-24
申请号：US10897508
申请日：2004-07-23
申请人： Fenyong Liu , Walter Dunn , Cassie Chou
发明人： Fenyong Liu , Walter Dunn , Cassie Chou
IPC分类号： C07K14/045 , C12N7/00 , C12N7/04 , C12Q20060101 , C12Q1/18 , C12Q1/70
CPC分类号： C12N7/00 , C07K14/005 , C12N2710/16122 , C12N2710/16161 , C12Q1/18 , G01N2333/045
摘要： A global functional analysis of HCMV genes is performed by constructing virus gene-deletion mutants and examining their growth phenotypes in different natural HCMV host cells. This systematic analysis of the HCMV genome identified 45 viral ORFs essential for viral replication and characterizes of 115 growth-dispensable viral genes. Of particular interest is the finding that HCMV encodes genes (temperance factors) that repress its own replication on a cell type-specific basis. In addition to HCMV, pathogen temperance may be a strategy employed by other infectious agents to enhance their long-term survivability within their respective host population.
摘要翻译：通过构建病毒基因缺失突变体并检查其在不同天然HCMV宿主细胞中的生长表型来进行HCMV基因的全局功能分析。对HCMV基因组的这种系统分析鉴定了病毒复制所必需的45种病毒ORF，并描述了115种可生长需要的病毒基因。特别感兴趣的是HCMV编码在细胞类型特异性基础上抑制其自身复制的基因（节制因子）的发现。除了HCMV之外，病原体温度可能是其他感染因子在其各自宿主群体中增强其长期存活能力的策略。

3. 发明授权

US06410704B1 Methods and compositions for the preparation and use of a herpes protease 失效
标题翻译：用于制备和使用疱疹蛋白酶的方法和组合物
公开(公告)号：US06410704B1
公开(公告)日：2002-06-25
申请号：US08176320
申请日：1994-01-03
申请人： Bernard Roizman , Fenyong Liu
发明人： Bernard Roizman , Fenyong Liu
IPC分类号： C07H2104
CPC分类号： C12N15/1133 , A61K38/00 , C07K14/005 , C07K16/085 , C12N9/503 , C12N15/86 , C12N2710/16622 , C12N2710/16643 , C12Q1/705 , Y10S435/815
摘要： The present invention relates to the identification and purification of a herpes protease and a nucleic acid segment coding for two proteins. The first protein is the herpes protease which is able to cleave itself and also cleave the second protein. This protease is required for the assembly of the herpes virus capsid, therefore is essential for replication. The second protein has previously been designated as the family of proteins in viral infected cells, ICP35. The protease and its substrates are encoded by overlapping nucleic acid segments. This invention also relates to a promoter sequence for the second protein. Methods are presented of producing a viral protease, screening a protease inhibitor which may be used in a drug designed for the treatment of herpes disease, methods for treating herpes and other viral infections wherein the virus employs a protease substantially similar to the herpes protease, for capsid production. Methods for detecting herpes infections and other viral infections are also disclosed.
摘要翻译：本发明涉及鉴定和纯化疱疹蛋白酶和编码两种蛋白质的核酸片段。第一种蛋白质是能够切割自身并且还切割第二种蛋白质的疱疹蛋白酶。这种蛋白酶是组装疱疹病毒衣壳所必需的，因此是复制所必需的。之前已经将第二种蛋白质命名为病毒感染细胞中的蛋白质家族，ICP35。蛋白酶及其底物通过重叠的核酸片段编码。本发明还涉及第二种蛋白质的启动子序列。提供了产生病毒蛋白酶的方法，筛选可用于治疗疱疹病毒的药物中的蛋白酶抑制剂，治疗疱疹和其它病毒感染的方法，其中病毒采用基本上类似于疱疹蛋白酶的蛋白酶，用于衣壳生产。还公开了检测疱疹感染和其他病毒感染的方法。

4. 发明授权

US5869248A Targeted cleavage of RNA using ribonuclease P targeting and cleavage sequences 失效
标题翻译：使用核糖核酸酶P靶向和切割序列靶向裂解RNA
公开(公告)号：US5869248A
公开(公告)日：1999-02-09
申请号：US702652
申请日：1996-11-06
申请人： Yan Yuan , Cecilia Guerrier-Takada , Sidney Altman , Fenyong Liu
发明人： Yan Yuan , Cecilia Guerrier-Takada , Sidney Altman , Fenyong Liu
IPC分类号： C12N15/09 , A61K9/127 , A61K31/70 , A61K35/76 , A61K38/00 , A61K47/48 , A61K48/00 , A61P31/12 , A61P35/02 , C07H21/02 , C07H21/04 , C12N9/22 , C12N15/113 , C12Q1/68
CPC分类号： C12N15/113 , A61K47/48776 , C12Q1/6813 , C12Q1/6827 , C12Q1/6848 , A61K38/00 , C12N2310/111 , C12N2310/126 , C12N2799/027
摘要： It has been discovered that any RNA can be targeted for cleavage by RNase P from prokaryotic or eukaryotic cells using a suitably designed oligonucleotide ("external guide sequence", or EGS) to form a hybrid with the target RNA, thereby creating a substrate for cleavage by RNase P in vitro. The EGS hydrogen bonds to the targeted RNA to form a partial tRNA like structure including the aminoacyl acceptor stem, the T stem and loop, and part of the D stem. An EGS can be modified both by changes in sequence and by chemical modifications to the nucleotides. The EGS can be a separate molecule or can be combined with an RNase P catalytic RNA sequence to form a single oligonucleotide molecule ("RNase P internal guide sequence" or RIGS). Methods are also disclosed to randomly select and to express a suitable EGS or RIGS in vivo to make a selected RNA a target for cleavage by a host cell RNase P or introduced RIGS, thus preventing expression of the function of the target RNA. The methods and compositions should be useful to prevent the expression of disease- or disorder-causing genes in vivo.
摘要翻译： PCT No.PCT / US95 / 02816 Sec。 371日期：1996年11月6日 102（e）日期1996年11月6日PCT 1994年3月7日PCT公布。公开号WO95 / 24489 日期1995年9月14日已经发现任何RNA可以使用合适设计的寡核苷酸（“外部引导序列”或EGS）从原核或真核细胞中靶向用RNA酶P切割以与靶RNA形成杂交体，由此在体外产生RNase P切割的底物。 EGS氢键与靶RNA形成部分tRNA样结构，包括氨酰受体茎，T干和环以及部分D茎。 EGS可以通过序列变化和对核苷酸的化学修饰来修饰。 EGS可以是单独的分子，也可以与RNase P催化RNA序列组合形成单个寡核苷酸分子（“RNase P内部导向序列”或RIGS）。还公开了在体内随机选择和表达合适的EGS或RIGS的方法，以使选定的RNA成为宿主细胞RNA酶P或引入的RIGS切割的靶标，从而阻止靶RNA功能的表达。该方法和组合物应该有用于在体内预防疾病或障碍引起的基因的表达。

5. 发明授权

US06849610B1 Polynucleotide ligands as anti-viral agents 有权
标题翻译：多核苷酸配体作为抗病毒剂
公开(公告)号：US06849610B1
公开(公告)日：2005-02-01
申请号：US09721543
申请日：2000-11-21
申请人： Fenyong Liu , Jun Wang , Hong Jiang
发明人： Fenyong Liu , Jun Wang , Hong Jiang
IPC分类号： A61K31/70 , A01N43/04 , C07H21/04
CPC分类号： A61K31/70
摘要： Infectious human cytomegalovirus (HCMV) were isolated in vitro from a pool of randomized sequences after sixteen or 21 cycles of selection and amplification. The ligands characterized exhibited high HCMV-binding affinity in vitro and effectively inhibited viral infection in tissue culture. Several ligands blocked viral entry. Their antiviral activity was also specific as the ligands only reacted with strains of HCMV, but not with the related herpes simplex virus 1 and human cells. Moreover, the ligands recognize several different epitopes. Thus, RNA ligands can function to bind to a human virus and block viral infection. The screening method may utilize the novel features of binding to intact infectious virus, partitioning the bound polynucleotides from unbound by passing through a porous filter, and enhancing the release of bound polynucleotides by treatment with protease.
摘要翻译：在16或21个循环选择和扩增后，从随机序列库中体外分离感染性巨细胞病毒（HCMV）。特征的配体体外表现出高的HCMV结合亲和力，并有效抑制组织培养中的病毒感染。几个配体阻止病毒进入。它们的抗病毒活性也是特异性的，因为配体仅与HCMV菌株反应，而不与相关的单纯疱疹病毒1和人细胞反应。此外，配体识别几个不同的表位。因此，RNA配体可以起到与人类病毒结合并阻断病毒感染的作用。筛选方法可以利用与完整感染性病毒结合的新特征，通过穿过多孔过滤器将结合的多核苷酸与未结合分开，并通过用蛋白酶处理增强结合的多核苷酸的释放。

6. 发明授权

US5478727A Methods and compositions for the preparation and use of a herpes protease 失效
公开(公告)号：US5478727A
公开(公告)日：1995-12-26
申请号：US832855
申请日：1992-02-07
申请人： Bernard Roizman , Fenyong Liu
发明人： Bernard Roizman , Fenyong Liu
IPC分类号： A61K38/00 , C07K14/035 , C07K16/08 , C12N9/50 , C12N15/113 , C12N15/869 , C12Q1/70 , C12N15/38 , C12Q1/00 , C12Q1/37
CPC分类号： C12N15/1133 , C07K14/005 , C07K16/085 , C12N15/86 , C12N9/503 , C12Q1/705 , A61K38/00 , C12N2710/16622 , C12N2710/16643 , Y10S435/815
摘要： The present invention relates to the identification and purification of a herpes protease and a nucleic acid segment coding for two proteins. The first protein is the herpes protease which is able to cleave itself and also cleave the second protein. This protease is required for the assembly of the herpes virus capsid, therefore is essential for replication. The second protein has previously been designated as the family of proteins in viral infected cells, ICP35. The protease and its substrates are encoded by overlapping nucleic acid segments. This invention also relates to a promoter sequence for the second protein. Methods are presented of producing a viral protease, screening a protease inhibitor which may be used in a drug designed for the treatment of herpes disease, methods for treating herpes and other viral infections wherein the virus employs a protease substantially similar to the herpes protease, for capsid production. Methods for detecting herpes infections and other viral infections are also disclosed.

7. 发明授权

US5728521A Targeted cleavage of RNA using eukaryotic ribonuclease P and external guide sequence 失效
标题翻译：使用真核生物核糖核酸酶P和外部引导序列靶向裂解RNA
公开(公告)号：US5728521A
公开(公告)日：1998-03-17
申请号：US215082
申请日：1994-03-18
申请人： Yan Yuan , Cecilia Guerrier-Takada , Sidney Altman , Fenyong Liu
发明人： Yan Yuan , Cecilia Guerrier-Takada , Sidney Altman , Fenyong Liu
IPC分类号： C12N15/09 , A61K9/127 , A61K31/70 , A61K35/76 , A61K38/00 , A61K47/48 , A61K48/00 , A61P31/12 , A61P35/02 , C07H21/02 , C07H21/04 , C12N9/22 , C12N15/113 , C12Q1/68 , C12P19/34
CPC分类号： C12N15/113 , A61K47/48776 , C12Q1/6813 , C12Q1/6827 , C12Q1/6848 , A61K38/00 , C12N2310/111 , C12N2310/126 , C12N2799/027
摘要： It has been discovered that any RNA can be targeted for cleavage by RNAase P from eukaryotic cells, for example, human RNAase P, using a suitably designed oligoribonucleotide ("external guide sequence", or EGS) to form a hybrid with the target RNA, thereby creating a substrate for cleavage by RNAase P in vitro. The EGS hydrogen bonds to the targeted RNA to form a partial tRNA like structure including the aminoacyl acceptor stem, the T stem and loop, and part of the D stem. The most efficient EGS with human RNAase P is the EGS in which the anticodon stem and loop was deleted. Modifications can also be made within the T-loop. Methods are also disclosed to randomly select and to express a suitable EGS in vivo to make a selected RNA a target for cleavage by the host cell RNAase P, thus preventing expression of the function of the target RNA. The methods and compositions should be useful to prevent the expression of disease-causing genes in vivo.
摘要翻译：已经发现，使用适当设计的寡核糖核苷酸（“外部引导序列”或EGS），可以使用RNA酶P从真核细胞例如人RNA酶P切割任何RNA，以形成与靶RNA的杂交体，从而在体外产生用RNA酶P切割的底物。 EGS氢键与靶RNA形成部分tRNA样结构，包括氨酰受体茎，T干和环以及部分D茎。具有人RNA酶P的最有效的EGS是其中反密码子茎和环被删除的EGS。修改也可以在T环内进行。还公开了在体内随机选择和表达合适的EGS以使所选择的RNA成为宿主细胞RNA酶P切割的靶标，从而阻止靶RNA功能的表达的方法。该方法和组合物应该有用于预防体内致病基因的表达。

8. 发明授权

US5624824A Targeted cleavage of RNA using eukaryotic ribonuclease P and external guide sequence 失效
标题翻译：使用真核生物核糖核酸酶P和外部引导序列靶向裂解RNA
公开(公告)号：US5624824A
公开(公告)日：1997-04-29
申请号：US207547
申请日：1994-03-07
申请人： Yan Yuan , Cecilia Guerrier-Takada , Sidney Altman , Fenyong Liu
发明人： Yan Yuan , Cecilia Guerrier-Takada , Sidney Altman , Fenyong Liu
IPC分类号： A61K47/48 , C12N15/113 , C12Q1/68 , C12P19/34 , A61K48/00 , C07H21/04
CPC分类号： C12N15/113 , A61K47/48776 , C12Q1/6813 , C12Q1/6827 , C12Q1/6848 , C12N2310/111 , C12N2310/126 , C12N2799/027
摘要： It has been discovered that any RNA can be targeted for cleavage by RNAase P from eukaryotic cells, for example, human RNAase P, using a suitably designed oligoribonucleotide ("external guide sequence", or EGS) to form a hybrid with the target RNA, thereby creating a substrate for cleavage by RNAase P in vitro. The EGS hydrogen bonds to the targeted RNA to form a partial tRNA like structure including the aminoacyl acceptor stem, the T stem and loop, and part of the D stem. The most efficient EGS with human RNAase P is the EGS in which the anticodon stem and loop was deleted. Modifications can also be made within the T-loop. Methods are also disclosed to randomly select and to express a suitable EGS in vivo to make a selected RNA a target for cleavage by the host cell RNAase P, thus preventing expression of the function of the target RNA. The methods and compositions should be useful to prevent the expression of disease-causing genes in vivo.
摘要翻译：已经发现，使用适当设计的寡核糖核苷酸（“外部引导序列”或EGS），可以使用RNA酶P从真核细胞例如人RNA酶P切割任何RNA，以形成与靶RNA的杂交体，从而在体外产生用RNA酶P切割的底物。 EGS氢键与靶RNA形成部分tRNA样结构，包括氨酰受体茎，T干和环以及部分D茎。具有人RNA酶P的最有效的EGS是其中反密码子茎和环被删除的EGS。修改也可以在T环内进行。还公开了在体内随机选择和表达合适的EGS以使所选择的RNA成为宿主细胞RNA酶P切割的靶标，从而阻止靶RNA功能的表达的方法。该方法和组合物应该有用于预防体内致病基因的表达。

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