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1. 发明授权

US08673557B2 Coupling endonucleases with end-processing enzymes drives high efficiency gene disruption 有权
标题翻译：将内切核酸酶与末端加工酶偶联可促进高效基因破坏
公开(公告)号：US08673557B2
公开(公告)日：2014-03-18
申请号：US13405183
申请日：2012-02-24
申请人： Andrew M. Scharenberg , Michael T. Certo , Kamila S. Gwiazda
发明人： Andrew M. Scharenberg , Michael T. Certo , Kamila S. Gwiazda
IPC分类号： C12Q1/68 , C12Q1/37
CPC分类号： C12N15/102 , A61K9/0019 , A61K35/28 , A61K38/45 , A61K38/465 , A61K38/52 , A61K2035/124 , C07K2319/60 , C12N9/1252 , C12N9/22 , C12N9/90 , C12N15/62 , C12N2800/80 , C12N2840/203 , A61K2300/00
摘要： The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.
摘要翻译：本公开内容涉及内切核酸酶与末端加工酶的共表达，目的是增强由内切核酸酶切割产生的多核苷酸末端的加工。

2. 发明申请

US20120276074A1 COUPLING ENDONUCLEASES WITH END-PROCESSING ENZYMES DRIVES HIGH EFFICIENCY GENE DISRUPTION 有权
标题翻译：具有末端加工酶的联合内切酶驱动高效基因破坏
公开(公告)号：US20120276074A1
公开(公告)日：2012-11-01
申请号：US13405183
申请日：2012-02-24
申请人： Andrew M. Scharenberg , Michael T. Certo , Kamila S. Gwiazda
发明人： Andrew M. Scharenberg , Michael T. Certo , Kamila S. Gwiazda
IPC分类号： C12N9/96 , A61P37/02 , A61P31/18 , C12N15/90 , A61K38/46
CPC分类号： C12N15/102 , A61K9/0019 , A61K35/28 , A61K38/45 , A61K38/465 , A61K38/52 , A61K2035/124 , C07K2319/60 , C12N9/1252 , C12N9/22 , C12N9/90 , C12N15/62 , C12N2800/80 , C12N2840/203 , A61K2300/00
摘要： The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.
摘要翻译：本公开内容涉及内切核酸酶与末端加工酶的共表达，目的是增强由内切核酸酶切割产生的多核苷酸末端的加工。

3. 发明授权

US08614300B2 Nucleic acids encoding a mut-T domain-containing polypeptide 失效
标题翻译：编码含有Mut-T结构域的多肽的核酸
公开(公告)号：US08614300B2
公开(公告)日：2013-12-24
申请号：US13416854
申请日：2012-03-09
申请人： Andrew M. Scharenberg
发明人： Andrew M. Scharenberg
IPC分类号： C07K16/40 , C07K16/46 , C07K16/00 , G01N33/53
CPC分类号： C07K14/705 , A61K48/00 , C12N9/14
摘要： The invention pertains to nucleic acids encoding a mutT domain-containing polypeptide, including fragments and biologically functional variants thereof. The invention also pertains to therapeutics and diagnostics involving the foregoing polypeptide and nucleic acids and agents that bind the foregoing polypeptide and nucleic acids. The invention also pertains to the identification of a novel mutT domain in human TrpC7, a polypeptide previously described as a putative calcium ion channel. Accordingly, the invention also pertains to methods and compositions for identifying agents useful in modulating mutT domain-mediated calcium or other ion transport in cells expressing a polypeptide comprising a mutT domain and a calcium or other ion channel.
摘要翻译：本发明涉及编码含有MutT结构域的多肽的核酸，包括其片段和生物功能变体。本发明还涉及涉及上述多肽的治疗学和诊断，以及结合前述多肽和核酸的核酸和试剂。本发明还涉及鉴定人trpC7中的新型mutT结构域，其是先前描述为假定的钙离子通道的多肽。因此，本发明还涉及用于鉴定可用于调节在表达包含mutT结构域和钙或其他离子通道的多肽的细胞中的mutT结构域介导的钙或其他离子转运的试剂的方法和组合物。

4. 发明授权

US08153400B1 Nucleic acids encoding a mutT domain-containing polypeptide 失效
标题翻译：编码含有MutT结构域的多肽的核酸
公开(公告)号：US08153400B1
公开(公告)日：2012-04-10
申请号：US09958184
申请日：2000-04-26
申请人： Andrew M. Scharenberg
发明人： Andrew M. Scharenberg
IPC分类号： C12N15/09
CPC分类号： C07K14/705 , A61K48/00 , C12N9/14
摘要： The invention pertains to nucleic acids encoding a mutT domain-containing polypeptide, including fragments and biologically functional variants thereof. The invention also pertains to therapeutics and diagnostics involving the foregoing polypeptide and nucleic acids and agents that bind the foregoing polypeptide and nucleic acids. The invention also pertains to the identification of a novel mutT domain in human TrpC7, a polypeptide previously described as a putative calcium ion channel. Accordingly, the invention also pertains to methods and compositions for identifying agents useful modulating mutT domain-mediated calcium or other ion transport in cells expressing a polypeptide comprising a mutT domain and a calcium or other ion channel.
摘要翻译：本发明涉及编码含有MutT结构域的多肽的核酸，包括其片段和生物功能变体。本发明还涉及涉及上述多肽的治疗学和诊断，以及结合前述多肽和核酸的核酸和试剂。本发明还涉及鉴定人trpC7中的新型mutT结构域，其是先前描述为假定的钙离子通道的多肽。因此，本发明还涉及用于鉴定在表达包含mutT结构域和钙或其他离子通道的多肽的细胞中有用调节mutT结构域介导的钙或其他离子转运的试剂的方法和组合物。

5. 发明授权

US10407672B2 Compositions and methods comprising the use of cell surface displayed homing endonucleases 有权
公开(公告)号：US10407672B2
公开(公告)日：2019-09-10
申请号：US12295201
申请日：2007-03-27
申请人： Andrew M. Scharenberg
发明人： Andrew M. Scharenberg
IPC分类号： C12N9/22 , C12N15/10
摘要： According to particular exemplary aspects, DNA target site binding and cleavage properties of native, variant or modified homing endonucleases (HE) (e.g., LAGLIDAG (LHE), HNH, His-Cys Box, GIY-YIG, I-SspI-type, and fusions, muteins or variants thereof) in solution are recapitulated on the cell surface (e.g., as assessed by flow cytometric analysis) to provide for novel cells expressing one or more cell surface HEs (e.g., expressing one or more HE binding and/or cleavage specificities), novel cell libraries, and high-throughput methods for assessing target site binding, target site cleavage. The rapid analysis of HE and LHE-DNA interactions on the cell surface with concurrent sorting options provides for high-throughput library screening affording rapid identification, analysis and isolation of novel HEs or LHEs having novel sequence specificities. Such novel sequence specificities, obtained by said methods provide novel methods for introducing targeted DNA-strand cleavage events, and novel chromatin immunoprecipitation methods (CHIP methods).

6. 发明申请

US20120237493A1 NUCLEIC ACIDS ENCODING A MUT-T DOMAIN-CONTAINING POLYPEPTIDE 失效
标题翻译：编码含有MUT-T域的多肽的核酸
公开(公告)号：US20120237493A1
公开(公告)日：2012-09-20
申请号：US13416854
申请日：2012-03-09
申请人： Andrew M. Scharenberg
发明人： Andrew M. Scharenberg
IPC分类号： A61K38/46 , C12N15/70 , C12N9/14 , C07K16/40 , C12N1/21 , G01N33/53 , G01N33/573 , C12Q1/34 , A61K31/7088 , C12N15/55 , C12Q1/68
CPC分类号： C07K14/705 , A61K48/00 , C12N9/14
摘要： The invention pertains to nucleic acids encoding a mutT domain-containing polypeptide, including fragments and biologically functional variants thereof. The invention also pertains to therapeutics and diagnostics involving the foregoing polypeptide and nucleic acids and agents that bind the foregoing polypeptide and nucleic acids. The invention also pertains to the identification of a novel mutT domain in human TrpC7, a polypeptide previously described as a putative calcium ion channel. Accordingly, the invention also pertains to methods and compositions for identifying agents useful in modulating mutT domain-mediated calcium or other ion transport in cells expressing a polypeptide comprising a mutT domain and a calcium or other ion channel.
摘要翻译：本发明涉及编码含有MutT结构域的多肽的核酸，包括其片段和生物功能变体。本发明还涉及涉及上述多肽的治疗学和诊断，以及结合前述多肽和核酸的核酸和试剂。本发明还涉及鉴定人trpC7中的新型mutT结构域，其是先前描述为假定的钙离子通道的多肽。因此，本发明还涉及用于鉴定可用于调节在表达包含mutT结构域和钙或其他离子通道的多肽的细胞中的mutT结构域介导的钙或其他离子转运的试剂的方法和组合物。

7. 发明申请

US20140148361A1 Generation and Expression of Engineered I-ONUI Endonuclease and Its Homologues and Uses Thereof 审中-公开
标题翻译：工程I-ONUI核酸内切酶及其同源物及其用途的生成与表达
公开(公告)号：US20140148361A1
公开(公告)日：2014-05-29
申请号：US13702972
申请日：2011-06-07
申请人： Barry L. Stoddard , Abigail Rose Lambert , Ryo Takeuchi , Andrew M. Scharenberg , Sarah Katherine Baxter
发明人： Barry L. Stoddard , Abigail Rose Lambert , Ryo Takeuchi , Andrew M. Scharenberg , Sarah Katherine Baxter
IPC分类号： C12N15/10
CPC分类号： C12N15/1037 , C07K2319/00 , C12N9/22 , C12N15/1034 , C12Q1/44 , G01N2333/922
摘要： The present disclosure provides compositions and methods for producing and expressing variant or engineered I-OnuI endonucleases, variant or engineered I-OnuI homologues, and hybrids of two I-OnuI or I-OnuI homologue domains that have a target site altered from the wild-type. A method for selecting a variant or engineered I-OnuI endonuclease, I-OnuI endonuclease homologue, and a hybrid of two I-OnuI or I-OnuI homologue domains that have a target site altered from the wild-type and directed to a site within a gene of interest is also provided. In addition, the present disclosure provides the crystal structure of the I-OnuI and I-LtrI endonucleases; the specificity profiles for both endonuclease for DNA binding and cleavage; the identity of amino acid residue positions in the I-OnuI and I-LtrI protein scaffold that determine DNA recognition specificity; methods for determining amino acid substitutions at those positions that alter DNA cleavage specificity; methods for the complete redesign of the DNA cleavage specificity of I-OnuI and its homologues for recognition and cleavage of a human gene of interest; and the relationship of the amino acid sequence, structure and specificity of I-OnuI to a collection of identifiable I-OnuI endonuclease homologues.
摘要翻译：本公开提供了用于产生和表达变体或工程化I-OnuI内切核酸酶，变体或工程化I-OnuI同源物的组合物和方法，以及两个I-OnuI或I-OnuI同系物结构域的杂交体，其具有从野生型类型。用于选择变体或工程化的I-OnuI核酸内切核酸酶，I-OnuI核酸内切酶同源物的方法，以及两个I-OnuI或I-OnuI同源结构域的杂交体，其具有从野生型改变的靶位点并引导至野生型还提供了感兴趣的基因。此外，本公开提供了I-OnuI和I-LtrI内切核酸酶的晶体结构; 核酸内切酶用于DNA结合和切割的特异性谱; 确定DNA识别特异性的I-OnuI和I-LtrI蛋白质支架中的氨基酸残基位置的身份; 在改变DNA裂解特异性的那些位置处测定氨基酸取代的方法; 完全重新设计I-OnuI及其同源物的DNA切割特异性的方法，用于识别和切割感兴趣的人类基因; 以及I-OnuI的氨基酸序列，结构和特异性与可鉴定的I-OnuI核酸内切酶同源物的集合的关系。

8. 发明授权

US08440638B2 Compositions and methods for modulating calcium flux, glucose homeostasis and apoptosis 有权
标题翻译：调节钙通量，葡萄糖体内平衡和细胞凋亡的组成和方法
公开(公告)号：US08440638B2
公开(公告)日：2013-05-14
申请号：US11658069
申请日：2005-07-20
申请人： John M. Denu , Andrew M. Scharenberg
发明人： John M. Denu , Andrew M. Scharenberg
IPC分类号： A61K31/7076 , A61K31/7052 , A61K31/455 , C07H19/167 , C07H19/20 , C07H19/173
CPC分类号： G01N33/6872 , G01N2500/04
摘要： Compositions and methods are disclosed which are effective for modulating glucose homeostasis, calcium ion flux and cell death in target cells.
摘要翻译：公开了组合物和方法，其有效调节靶细胞中的葡萄糖体内平衡，钙离子通量和细胞死亡。

9. 发明申请

US20090162937A1 COMPOSITIONS AND METHODS COMPRISING THE USE OF CELL SURFACE DISPLAYED HOMING ENDONUCLEASES 审中-公开
标题翻译：包含使用显示出内切子的细胞表面的组合物和方法
公开(公告)号：US20090162937A1
公开(公告)日：2009-06-25
申请号：US12295201
申请日：2007-03-27
申请人： Andrew M. Scharenberg
发明人： Andrew M. Scharenberg
IPC分类号： C12N15/87 , C12N9/24 , C40B30/04 , C40B40/02
CPC分类号： C12N9/22 , C12N15/1037
摘要： According to particular exemplary aspects, DNA target site binding and cleavage properties of native, variant or modified homing endonucleases (HE) (e.g., LAGLIDAG (LHE), HNH, His-Cys Box, GIY-YIG, I-SspI-type, and fusions, muteins or variants thereof) in solution are recapitulated on the cell surface (e.g., as assessed by flow cytometric analysis) to provide for novel cells expressing one or more cell surface HEs (e.g., expressing one or more HE binding and/or cleavage specificities), novel cell libraries, and high-throughput methods for assessing target site binding, target site cleavage. The rapid analysis of HE and LHE-DNA interactions on the cell surface with concurrent sorting options provides for high-throughput library screening affording rapid identification, analysis and isolation of novel HEs or LHEs having novel sequence specificities. Such novel sequence specificities, obtained by said methods provide novel methods for introducing targeted DNA-strand cleavage events, and novel chromatin immunoprecipitation methods (CHIP methods).
摘要翻译：根据具体示例性方面，天然，变体或修饰的归巢内切核酸酶（HE）（例如LAGLIDAG（LHE），HNH，His-Cys Box，GIY-YIG，I-SspI型和融合物，突变蛋白或其变体）在细胞表面（例如，通过流式细胞术分析评估），以提供表达一种或多种细胞表面HE的新细胞（例如，表达一种或多种HE结合和/或切割特异性），新型细胞库和用于评估靶位点结合，靶位点切割的高通量方法。 HE和LHE-DNA在细胞表面上的相互作用的快速分析与并行排序选项提供了高通量文库筛选，可以快速鉴定，分析和分离具有新序列特异性的新型HE或LHE。通过所述方法获得的这种新型序列特异性提供了引入目标DNA链裂解事件的新方法和新颖的染色质免疫沉淀方法（CHIP方法）。

10. 发明申请

US20080249059A1 Compositions and Methods for modulating Calcium Flux, Glucose Homeostasis and Apoptosis 有权
标题翻译：调节钙通量，葡萄糖稳态和细胞凋亡的组成和方法
公开(公告)号：US20080249059A1
公开(公告)日：2008-10-09
申请号：US11658069
申请日：2005-07-20
申请人： John M. Denu , Andrew M. Scharenberg
发明人： John M. Denu , Andrew M. Scharenberg
IPC分类号： A61K31/7076 , A61K31/4406 , C12N5/06 , C07H21/04 , C12Q1/02
CPC分类号： G01N33/6872 , G01N2500/04
摘要： Compositions and methods are disclosed which are effective for modulating glucose homeostasis, calcium ion flux and cell death in target cells.
摘要翻译：公开了组合物和方法，其有效调节靶细胞中的葡萄糖体内平衡，钙离子通量和细胞死亡。

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