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1. 发明授权

US09068969B2 Cell based methods and systems for the identification of RNA regulatory sequences and compounds that modulate their functions 有权
标题翻译：用于鉴定调节其功能的RNA调节序列和化合物的基于细胞的方法和系统
公开(公告)号：US09068969B2
公开(公告)日：2015-06-30
申请号：US11813027
申请日：2005-12-27
申请人： Christopher R. Trotta
发明人： Matthew C. Pelligrini
IPC分类号： C12Q1/68 , G01N33/50 , C12N15/10 , C07H21/02 , C07H21/04
CPC分类号： G01N33/5008 , C12N15/1086 , C12Q1/68
摘要： The present invention is directed to methods of screening for a small molecule that modulates the ability of a RNA regulatory sequence to inhibit mRNA translation in a mammalian cell comprising incubating the mammalian cell expressing a reporter mRNA and the RNA regulatory sequence in the presence of the small molecule, wherein the RNA regulatory sequence is not attached to the reporter mRNA; and monitoring a reporter protein signal produced by the reporter mRNA, wherein a change in the signal of the reporter protein in the presence of the small molecule compared to the reporter protein signal in the absence of the small molecule indicates the small molecule modulates the ability of the RNA regulatory sequence to inhibit mRNA translation.
摘要翻译：本发明涉及筛选调节哺乳动物细胞中RNA调节序列抑制mRNA翻译的能力的小分子的方法，其包括在小的存在下孵育表达报道mRNA的哺乳动物细胞和RNA调节序列分子，其中RNA调节序列不连接到报告基因mRNA; 并监测由报道mRNA产生的报道蛋白信号，其中在不存在小分子的情况下，与小报告蛋白信号相比，在小分子存在下报道蛋白信号的变化表明小分子调节 RNA调控序列来抑制mRNA翻译。

2. 发明授权

US08076353B2 Inhibition of VEGF translation 有权
标题翻译： VEGF翻译的抑制
公开(公告)号：US08076353B2
公开(公告)日：2011-12-13
申请号：US11765871
申请日：2007-06-20
申请人： Liangxian Cao , Thomas W. Davis , Charles M. Romfo , Christopher R. Trotta
发明人： Liangxian Cao , Thomas W. Davis , Charles M. Romfo , Christopher R. Trotta
IPC分类号： A61K31/437
CPC分类号： A61K31/437 , A61K31/497 , A61K31/5377 , A61K31/541 , A61K31/551 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158
摘要： In accordance with the present invention, methods for inhibiting the translation of VEGF and methods for decreasing VEGF level by inhibiting VEGF translation are provided. In another aspect of the invention, compounds that inhibit the 5′-UTR-dependent translation of VEGF and methods for identifying such compounds are provided.
摘要翻译：根据本发明，提供了通过抑制VEGF翻译来抑制VEGF翻译的方法和降低VEGF水平的方法。在本发明的另一方面，提供了抑制VEGF的5'-UTR-依赖性翻译的化合物和用于鉴定这些化合物的方法。

3. 发明授权

US07829503B2 Methods of identifying compounds that target tRNA splicing endonuclease and uses of said compounds as anti-fungal agents 有权
标题翻译：鉴定靶向tRNA剪接核酸内切酶的化合物的方法和所述化合物用作抗真菌剂的方法
公开(公告)号：US07829503B2
公开(公告)日：2010-11-09
申请号：US10551304
申请日：2004-03-26
申请人： Christopher R. Trotta
发明人： Christopher R. Trotta
IPC分类号： C40B30/06 , C40B40/08 , A61K31/00
CPC分类号： C40B30/06 , C12Q1/6813 , C12Q1/6897 , C12Q2539/105
摘要： The present invention relates to a method for screening and identifying compounds that modulate the activity of a fungal tRNA splicing endonuclease. In particular, the invention provides assays for the identification of compounds that inhibit or reduce the activity of a fungal tRNA splicing endonuclease. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads useful for preventing, treating, managing and/or ameliorating a fungal infection or fungal infestation or one or more symptoms thereof.
摘要翻译：本发明涉及筛选和鉴定调节真菌tRNA剪接核酸内切酶活性的化合物的方法。特别地，本发明提供了用于鉴定抑制或降低真菌tRNA剪接内切核酸酶活性的化合物的测定。本发明的方法提供了一种用于高通量筛选化合物文库的简单敏感的测定法，以鉴定可用于预防，治疗，管理和/或改善真菌感染或真菌侵袭或其一种或多种症状的药物引线。

4. 发明申请

US20100136710A1 RNA processing protein complexes and uses thereof 有权
标题翻译： RNA加工蛋白复合物及其用途
公开(公告)号：US20100136710A1
公开(公告)日：2010-06-03
申请号：US12317899
申请日：2008-12-30
申请人： Christopher R. Trotta , Sergey Paushkin
发明人： Christopher R. Trotta , Sergey Paushkin
IPC分类号： G01N33/53 , C12N9/16 , C07K16/00 , C07H21/04
CPC分类号： C12Q1/6897 , C07K14/47 , C12N9/22
摘要： The invention provides human protein complexes with endonuclease activity. In particular, the invention provides human protein complexes with tRNA splicing endonuclease activity and/or 3′ end pre-mRNA endonuclease activity. The invention also provides a splice variant of human Sen2, namely human Sen2deltaEx8, and human protein complexes comprising human Sen2deltaEx8. The human Sen2deltaEx8 complexes have pre-tRNA cleavage activity and/or 3′ end pre-mRNA endonuclease activity. The invention also provides human protein complexes with pre-ribosomal RNA cleavage activity. The invention also provides antibodies that immunospecifically bind to a complex described herein or a component thereof, and methods of diagnosing, preventing, treating, managing or ameliorating a disorder utilizing such antibodies. The present invention also provides methods utilizing the complexes described herein, inter alia, in screening, diagnosis, and therapy. The invention further provides methods of preparing and purifying the complexes. The present invention further provides methods of identifying a compound that modulates the expression of a component of a complex described herein, the formation of a complex described herein or the activity of a complex described herein, and methods of preventing, treating, managing or ameliorating a disorder, such as a proliferative disorder, or a symptom thereof utilizing a compound identified in accordance with the methods.
摘要翻译：本发明提供具有内切核酸酶活性的人蛋白复合物。特别地，本发明提供具有tRNA剪接核酸内切酶活性和/或3'末端pre-mRNA内切酶活性的人蛋白复合物。本发明还提供人Sen2的剪接变体，即人Sen2deltaEx8，以及包含人Sen2deltaEx8的人蛋白复合物。人类Sen2deltaEx8复合物具有pre-tRNA切割活性和/或3'末端pre-mRNA内切核酸酶活性。本发明还提供具有前核糖体RNA切割活性的人蛋白复合物。本发明还提供了免疫特异性结合本文所述的复合物或其组分的抗体，以及利用此类抗体诊断，预防，治疗，治疗或改善病症的方法。本发明还提供了利用本文所述的复合物，特别是在筛选，诊断和治疗中的方法。本发明还提供了制备和纯化复合物的方法。本发明还提供了鉴定调节本文所述复合物组分的表达，本文所述的复合物的形成或本文所述的复合物的活性的化合物的方法，以及预防，治疗，治疗或改善疾病，例如增殖性疾病，或其症状，利用根据该方法鉴定的化合物。

5. 发明授权

US09068234B2 Methods and agents for screening for compounds capable of modulating gene expression 有权
标题翻译：用于筛选能够调节基因表达的化合物的方法和试剂
公开(公告)号：US09068234B2
公开(公告)日：2015-06-30
申请号：US10895393
申请日：2004-07-21
申请人： Liangxian Cao , Anuradha Mehta , Nikolai A. Naryshkin , Matthew C. Pellegrini , Charles M. Romfo , Panayiota Trifillis , Christopher R. Trotta
发明人： Liangxian Cao , Anuradha Mehta , Nikolai A. Naryshkin , Matthew C. Pellegrini , Charles M. Romfo , Panayiota Trifillis , Christopher R. Trotta
IPC分类号： C12Q1/68 , C07H21/02
CPC分类号： G01N33/5023 , C12Q1/6897 , G01N33/74 , G01N2333/49 , G01N2333/90241
摘要： The invention relates to the fields of screening assays, compounds, and methods for altering gene expression and protein levels. In particular, the invention includes assays to screen for agents capable of modulating gene expression in a UTR-dependent manner and agents capable of modulating gene expression.
摘要翻译：本发明涉及筛选测定领域，化合物以及用于改变基因表达和蛋白质水平的方法。具体地，本发明包括筛选能够以UTR依赖性方式调节基因表达的试剂和能够调节基因表达的试剂。

6. 发明授权

US08278085B2 RNA processing protein complexes and uses thereof 有权
标题翻译： RNA加工蛋白复合物及其用途
公开(公告)号：US08278085B2
公开(公告)日：2012-10-02
申请号：US12317899
申请日：2008-12-30
申请人： Christopher R. Trotta , Sergey Paushkin
发明人： Christopher R. Trotta , Sergey Paushkin
IPC分类号： C07K14/00 , C12N9/16 , C12P21/00 , C12Q1/44
CPC分类号： C12Q1/6897 , C07K14/47 , C12N9/22
摘要： The invention provides human protein complexes with endonuclease activity, including tRNA splicing endonuclease activity and 3′ end pre-mRNA endonuclease activity, and pre-ribosomal RNA cleavage activity. The invention also provides a splice variant of human Sen2, and human protein complexes comprising the variant. The invention provides human protein complexes with pre-ribosomal RNA cleavage activity. The invention also provides antibodies that immunospecifically bind to a complex described herein or a component thereof, and uses of such antibodies. The present invention also provides methods of preparing and purifying the complexes and uses of the complexes inter alia, in screening, diagnosis, and therapy. The present invention further provides methods of identifying a compound that modulates the expression of a component of a complex described herein, the formation of a complex described herein or the activity of a complex described herein, and methods of preventing, treating, managing or ameliorating a disorder, such as a proliferative disorder, or a symptom thereof utilizing such a compound.
摘要翻译：本发明提供具有核酸内切酶活性的人蛋白复合物，包括tRNA剪接核酸内切酶活性和3'末端前mRNA内切核酸酶活性，以及前核糖体RNA切割活性。本发明还提供了人Sen2的剪接变体和包含该变体的人蛋白复合物。本发明提供具有前核糖体RNA切割活性的人蛋白复合物。本发明还提供免疫特异性结合本文所述的复合物或其组分的抗体，以及这些抗体的用途。本发明还提供了制备和纯化复合物的方法以及复合物的用途，特别是在筛选，诊断和治疗中。本发明进一步提供了鉴定调节本文所述复合物组分的表达，本文所述的复合物的形成或本文所述的复合物的活性的化合物的方法，以及预防，治疗，治疗或改善障碍，例如增殖性疾病，或其利用这种化合物的症状。

7. 发明申请

US20110172108A1 TARGETING ENZYMES OF THE tRNA SPLICING PATHWAY FOR IDENTIFICATION OF ANTI-FUNGAL AND/OR ANTI-PROLIFERATIVE MOLECULES 审中-公开
标题翻译：用于鉴定抗真菌和/或抗增殖分子的tRNA分离途径的靶向酶
公开(公告)号：US20110172108A1
公开(公告)日：2011-07-14
申请号：US12753590
申请日：2010-04-02
申请人： Christopher R. Trotta
发明人： Christopher R. Trotta
IPC分类号： C40B30/00 , C12N9/16 , C12Q1/68
CPC分类号： C12Q1/6897 , C12N15/1034 , C12Q1/18 , G01N33/5011 , G01N2333/9015 , C12Q2539/105
摘要： The present invention relates to a method for screening and identifying compounds that modulate the activity of one or more components in the tRNA splicing pathway. In particular the invention relates to a method for screening and identifying compounds that modulate the activity tRNA splicing endonuclease and/or tRNA splicing ligase. The invention provides assays for the identification of compounds that inhibit animalia tRNA splicing endonuclease and/or animalia tRNA splicing ligase. The invention also provides assays for the identification of compounds that inhibit fungal tRNA splicing endonuclease and/or fungal tRNA splicing ligase. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads useful for treating and/or preventing cancer and/or fungal infections.
摘要翻译：本发明涉及筛选和鉴定调节tRNA剪接途径中一种或多种组分的活性的化合物的方法。特别地，本发明涉及筛选和鉴定调节活性tRNA剪接内切核酸酶和/或tRNA剪接连接酶的化合物的方法。本发明提供了用于鉴定抑制动物TRNA剪接内切核酸酶和/或动物TRNA剪接连接酶的化合物的测定。本发明还提供了用于鉴定抑制真菌tRNA剪接内切核酸酶和/或真菌tRNA剪接连接酶的化合物的测定法。本发明的方法提供了一种用于高通量筛选化合物文库以鉴定可用于治疗和/或预防癌症和/或真菌感染的药物引线的简单敏感的测定法。

8. 发明授权

US07939468B2 Methods of identifying compounds that target tRNA splicing endonuclease and uses of said compounds as anti-proliferative agents 有权
标题翻译：鉴定靶向tRNA剪接核酸内切酶的化合物的方法和所述化合物用作抗增殖剂的方法
公开(公告)号：US07939468B2
公开(公告)日：2011-05-10
申请号：US12756786
申请日：2010-04-08
申请人： Christopher R. Trotta
发明人： Christopher R. Trotta
IPC分类号： C12Q1/68 , C40B30/06 , C40B40/08 , A61K31/00
CPC分类号： C12N9/22 , C12Q1/6897 , C12Q2539/105
摘要： The present invention relates to a method for screening and identifying compounds that modulate the activity tRNA splicing endonuclease. In particular, the invention provides assays for the identification of compounds that inhibit animalia tRNA splicing endonuclease. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads useful for treating and/or preventing cancer.
摘要翻译：本发明涉及筛选和鉴定调节活性tRNA剪接核酸内切酶的化合物的方法。特别地，本发明提供了用于鉴定抑制动物TRNA剪接内切核酸酶的化合物的测定。本发明的方法提供了用于鉴定可用于治疗和/或预防癌症的药物引用的化合物文库的高通量筛选的简单，灵敏的测定。

9. 发明申请

US20100267035A1 METHODS OF IDENTIFYING COMPOUNDS THAT TARGET tRNA SPLICING ENDONUCLEASE AND USES OF SAID COMPOUNDS AS ANTI-PROLIFERATIVE AGENTS 有权
标题翻译：鉴定目标tRNA分离内切酶的化合物的方法和作为抗增殖剂的合成化合物的用途
公开(公告)号：US20100267035A1
公开(公告)日：2010-10-21
申请号：US12756786
申请日：2010-04-08
申请人： Christopher R. Trotta
发明人： Christopher R. Trotta
IPC分类号： C12Q1/68
CPC分类号： C12N9/22 , C12Q1/6897 , C12Q2539/105
摘要： The present invention relates to a method for screening and identifying compounds that modulate the activity tRNA splicing endonuclease. In particular, the invention provides assays for the identification of compounds that inhibit animalia tRNA splicing endonuclease. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads useful for treating and/or preventing cancer.
摘要翻译：本发明涉及筛选和鉴定调节活性tRNA剪接核酸内切酶的化合物的方法。特别地，本发明提供了用于鉴定抑制动物TRNA剪接内切核酸酶的化合物的测定。本发明的方法提供了用于鉴定可用于治疗和/或预防癌症的药物引用的化合物文库的高通量筛选的简单，灵敏的测定。

10. 发明申请

US20080318222A1 Cell Based Methods And Systems For The Identification Of Rna Regulatory Sequences And Compounds That Modulate Their Functions 有权
标题翻译：基于细胞的方法和系统用于鉴定调节其功能的Rna调节序列和化合物
公开(公告)号：US20080318222A1
公开(公告)日：2008-12-25
申请号：US11813027
申请日：2005-12-27
申请人： Matthew C. Pelligrini , Christopher R. Trotta
发明人： Matthew C. Pelligrini , Christopher R. Trotta
IPC分类号： C12Q1/68 , C12N5/10
CPC分类号： G01N33/5008 , C12N15/1086 , C12Q1/68
摘要： The present invention is directed to an in vivo method for screening for and/or identifying RNA regulatory sequences involved in translational control. The method includes: culturing cells including: (i) a translational system; (ii) a reporter mRNA; and (iii) an RNA test sequence under suitable conditions for translation of the reporter mRNA, wherein the RNA test sequence is not attached to the reporter mRNA. The method also includes measuring the effect of the test sequence on the translation of the reporter mRNA, wherein a test sequence that modifies the translation of the reporter mRNA includes an RNA regulatory element. The invention also provides methods and systems for screening for and/or identifying test compounds that modulate the regulatory activity of an RNA regulatory sequence. This method includes culturing cells including (i) a translation system; (ii) a reporter mRNA; and (iii) an RNA regulatory sequence in the presence of at least one test compound, wherein the RNA regulatory sequence is not attached to the reporter mRNA. The ability of the test compound to affect the interaction between the RNA regulatory sequence and at least one component of the translation system is sought to be determined. The method further includes monitoring for the effect of the test compound on the this interaction, wherein a compound that modifies this interaction is a drug candidate.
摘要翻译：本发明涉及用于筛选和/或鉴定涉及翻译控制的RNA调节序列的体内方法。该方法包括：培养细胞，包括：（i）翻译系统; （ii）报告mRNA; 和（iii）在用于翻译报告mRNA的合适条件下的RNA测试序列，其中RNA测试序列不与报道mRNA连接。该方法还包括测量测试序列对报告mRNA的翻译的影响，其中修饰报道mRNA的翻译的测试序列包括RNA调节元件。本发明还提供用于筛选和/或鉴定调节RNA调节序列的调节活性的测试化合物的方法和系统。该方法包括培养细胞，包括（i）翻译系统; （ii）报告mRNA; 和（iii）在至少一种测试化合物存在下的RNA调节序列，其中所述RNA调节序列不与报道mRNA连接。试图确定测试化合物影响RNA调节序列与翻译系统的至少一个组分之间的相互作用的能力。该方法还包括监测测试化合物对该相互作用的影响，其中修饰该相互作用的化合物是候选药物。

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