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1. 发明授权

US09284562B2 Biological circuit chemotactic converters 有权
标题翻译：生物电路趋化转换器
公开(公告)号：US09284562B2
公开(公告)日：2016-03-15
申请号：US13512453
申请日：2010-11-30
申请人： James J. Collins , Timothy Kuan-Ta Lu
发明人： James J. Collins , Timothy Kuan-Ta Lu
IPC分类号： C12N15/00 , C12N15/09 , C07H21/04 , C12Q1/68 , H03M1/66 , H03M1/12 , C12N15/63
CPC分类号： C12N15/63 , C12N15/635
摘要： Described herein are novel biological circuit chemotactic converter that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for detecting and converting external inputs, such as chemoattractants, into outputs that allow for autonomous chemotaxis in cellular systems. Flexibility in these biological circuit chemotactic converter is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create network systems that regulate chemotactic responses based on the combination and nature of input signals received.
摘要翻译：这里描述的是利用诸如遗传拨动开关和单一转换存储器模块（SIMM）等模块化组件的新型生物电路趋化转换器，用于检测和转换诸如化学引诱剂的外部输入到允许在细胞系统中自主趋化的输出。这些生物电路趋化转换器的灵活性通过将各个模块化组件即SIMM和遗传拨动开关组合在一起来提供。这些生物转换器开关可以组合在各种网络拓扑中，以创建基于所接收的输入信号的组合和性质来调节趋化反应的网络系统。

2. 发明申请

US20110097721A1 IN VIVO GENE SENSORS 有权
标题翻译： VIVO基因传感器
公开(公告)号：US20110097721A1
公开(公告)日：2011-04-28
申请号：US12867537
申请日：2009-02-17
申请人： James J. Collins , Timothy Kuan-Ta Lu
发明人： James J. Collins , Timothy Kuan-Ta Lu
IPC分类号： C12Q1/68 , C12N15/00
CPC分类号： C12N15/1086 , C12N15/111 , C12N15/63 , C12N2310/111 , C12N2320/50
摘要： Described are methods and compositions for the detection of target genes. The inventors have developed a synthetic nucleic acid sensor-effector gene circuit. In cells without a target gene, the circuit suppresses e.g., effector production, but in the presence of the target gene the suppression is subject to competition, such that the synthetic sensor is de-repressed and permits expression of the effector gene. The methods and compositions described further permit the selective expression of an effector gene in those cells expressing the target gene. In this manner, cells expressing a target gene can be selectively targeted for treatment or elimination. In certain aspects, the methods and compositions described permit the selective expression of an agent such as a therapeutic gene product, in a specifically targeted population of cells in an organism.
摘要翻译：描述了用于检测靶基因的方法和组合物。本发明人开发了合成核酸传感器 - 效应子基因电路。在没有靶基因的细胞中，电路抑制例如效应子产生，但是在靶基因的存在下，抑制受到竞争，使得合成传感器被去抑制并且允许效应基因的表达。所描述的方法和组合物进一步允许在表达靶基因的那些细胞中选择性表达效应基因。以这种方式，表达靶基因的细胞可以选择性地靶向用于治疗或消除。在某些方面，所描述的方法和组合允许在生物体中的特定靶细胞群中选择性地表达诸如治疗性基因产物的试剂。

3. 发明授权

US10676721B2 Bacteriophages expressing antimicrobial peptides and uses thereof 有权
公开(公告)号：US10676721B2
公开(公告)日：2020-06-09
申请号：US13224776
申请日：2011-09-02
申请人： James J. Collins , Michael Koeris , Timothy Kuan-Ta Lu , Gregory Stephanopoulos , Christopher Jongsoo Yoon
发明人： James J. Collins , Michael Koeris , Timothy Kuan-Ta Lu , Tanguy My Chau , Gregory Stephanopoulos , Christopher Jongsoo Yoon
IPC分类号： C12N7/00 , A61K35/76 , A61K38/17 , C07K14/435 , C07K14/46 , C12N9/50
摘要： The present invention is generally related to engineered bacteriophages expressing antimicrobial peptides or lytic enzymes or fragments thereof for targeting a broad spectrum of bacterial hosts, and for the long-term suppression of bacterial phage resistance for reducing bacterial infections. In some embodiments, bacteriophages express antimicrobial peptides or antimicrobial polypeptides (e.g. phage lytic enzymes) which are secreted from the host bacteria, or alternatively released upon lysis of the bacterial host cell. Aspects of the present invention also relate to the use of the engineered bacteriophages for the reduction of bacterial infections, both in a subject or for bioremediation purposes, in clinical settings and wound healing.

4. 发明授权

US09624554B2 Modular nucleic acid-based circuits for counters, binary operations, memory, and logic 有权
公开(公告)号：US09624554B2
公开(公告)日：2017-04-18
申请号：US14135009
申请日：2013-12-19
申请人： James J. Collins , Timothy Kuan-Ta Lu
发明人： James J. Collins , Timothy Kuan-Ta Lu
IPC分类号： G06G7/48 , G06G7/58 , G01N33/48 , G01N31/00 , C12Q1/68 , C12N15/63
CPC分类号： C12Q1/6897 , C12N15/63 , C12N15/635 , C12Q2521/507
摘要： We have created novel engineered genetic counter designs and methods of use thereof that utilize DNA recombinases to provide modular systems, termed single invertase memory modules (SIMMs), for encoding memory in cells and cellular systems. Our designs are easily extended to compute to high numbers, by utilizing the >100 known recombinases to create subsequent modules. Flexibility in our engineered genetic counter designs is provided by daisy-chaining individual modular components, i.e., SIMMs together. These modular components of the engineered genetic counters can be combined in other network topologies to create circuits that perform, amongst other things, logic and memory. Our novel engineered genetic counter designs allow for the maintenance of memory and provide the ability to count between discrete states by expressing the recombinases between their cognate recognition sites.

5. 发明申请

US20150050717A1 BACTERIOPHAGES EXPRESSING ANTIMICROBIAL PEPTIDES AND USES THEREOF 审中-公开
标题翻译：表达抗真菌肽的特异性及其用途
公开(公告)号：US20150050717A1
公开(公告)日：2015-02-19
申请号：US13224776
申请日：2011-09-02
申请人： James J. Collins , Michael Koeris , Timothy Kuan-Ta Lu , Gregory Stephanopoulos , Christopher Yoon
发明人： James J. Collins , Michael Koeris , Timothy Kuan-Ta Lu , Tanguy My Chau , Gregory Stephanopoulos , Christopher Yoon
IPC分类号： C12N7/00 , A61K35/76
摘要： The present invention is generally related to engineered bacteriophages expressing antimicrobial peptides or lytic enzymes or fragments thereof for targeting a broad spectrum of bacterial hosts, and for the long-term suppression of bacterial phage resistance for reducing bacterial infections. In some embodiments, bacteriophages express antimicrobial peptides or antimicrobial polypeptides (e.g. phage lytic enzymes) which are secreted from the host bacteria, or alternatively released upon lysis of the bacterial host cell. Aspects of the present invention also relate to the use of the engineered bacteriophages for the reduction of bacterial infections, both in a subject or for bioremediation purposes, in clinical settings and wound healing.
摘要翻译：本发明通常涉及表达用于靶向广谱细菌宿主的抗微生物肽或溶解酶或其片段的工程化噬菌体，以及长期抑制细菌噬菌体抗性以减少细菌感染。在一些实施方案中，噬菌体表达从宿主细菌分泌的抗微生物肽或抗微生物多肽（例如噬菌体裂解酶），或者在细菌宿主细胞裂解时释放。本发明的方面还涉及在临床环境和伤口愈合中使用工程化噬菌体来减少细菌感染，在受试者中或用于生物修复目的。

6. 发明申请

US20130009799A1 BIOLOGICAL ANALOG-TO-DIGITAL AND DIGITAL-TO-ANALOG CONVERTERS 有权
标题翻译：生物数字到数字和数字到模拟转换器
公开(公告)号：US20130009799A1
公开(公告)日：2013-01-10
申请号：US13512449
申请日：2010-11-30
申请人： James J. Collins , Timothy Kuan-Ta Lu
发明人： James J. Collins , Timothy Kuan-Ta Lu
IPC分类号： H03M1/66 , H03M1/12
CPC分类号： G06N3/002 , H03M1/361 , H03M1/74
摘要： Described herein are novel biological converter switches that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for converting analog inputs to digital outputs, and digital inputs to analog outputs, in cells and cellular systems. Flexibility in these biological converter switches is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create circuits that act, for example, as switchboards, and regulate the production of an output product(s) based on the combination and nature of input signals received.
摘要翻译：这里描述的是利用诸如遗传拨动开关和单个转换存储器模块（SIMM）的模块化组件的新型生物转换器开关，用于将模拟输入转换成数字输出，以及在单元和蜂窝系统中将模拟输出的数字输入转换成模拟输出。这些生物转换器开关的灵活性通过将各个模块化组件即SIMM和遗传拨动开关组合在一起来提供。这些生物转换器开关可以组合在各种网络拓扑中，以产生例如作为配电板起作用的电路，并且基于所接收的输入信号的组合和性质来调节输出产品的生产。

7. 发明授权

US08329889B2 In vivo gene sensors 有权
标题翻译：体内基因传感器
公开(公告)号：US08329889B2
公开(公告)日：2012-12-11
申请号：US12867537
申请日：2009-02-17
申请人： James J. Collins , Timothy Kuan-Ta Lu
发明人： James J. Collins , Timothy Kuan-Ta Lu
IPC分类号： C07H21/04
CPC分类号： C12N15/1086 , C12N15/111 , C12N15/63 , C12N2310/111 , C12N2320/50
摘要： Described are methods and compositions for the detection of target genes. The inventors have developed a synthetic nucleic acid sensor-effector gene circuit. In cells without a target gene, the circuit suppresses e.g., effector production, but in the presence of the target gene the suppression is subject to competition, such that the synthetic sensor is de-repressed and permits expression of the effector gene. The methods and compositions described further permit the selective expression of an effector gene in those cells expressing the target gene. In this manner, cells expressing a target gene can be selectively targeted for treatment or elimination. In certain aspects, the methods and compositions described permit the selective expression of an agent such as a therapeutic gene product, in a specifically targeted population of cells in an organism.
摘要翻译：描述了用于检测靶基因的方法和组合物。本发明人开发了合成核酸传感器 - 效应子基因电路。在没有靶基因的细胞中，电路抑制例如效应子产生，但是在靶基因的存在下，抑制受到竞争，使得合成传感器被去抑制并且允许效应基因的表达。所描述的方法和组合物进一步允许在表达靶基因的那些细胞中选择性表达效应基因。以这种方式，表达靶基因的细胞可以选择性地靶向用于治疗或消除。在某些方面，所描述的方法和组合允许在生物体中的特定靶细胞群中选择性地表达诸如治疗性基因产物的试剂。

8. 发明授权

US08182804B1 Engineered enzymatically active bacteriophages and methods of uses thereof 有权
标题翻译：工程化酶活性噬菌体及其应用方法
公开(公告)号：US08182804B1
公开(公告)日：2012-05-22
申请号：US11662551
申请日：2005-09-12
申请人： James J Collins , Hideki Kobayashi , Mads Kearn , Michihiro Araki , Ari Friedland , Timothy Kuan-Ta Lu
发明人： James J Collins , Hideki Kobayashi , Mads Kearn , Michihiro Araki , Ari Friedland , Timothy Kuan-Ta Lu
IPC分类号： A01N63/00 , C12N15/74 , A61K48/00
CPC分类号： C12N9/2437 , A61L2/16 , C07K14/005 , C07K2319/00 , C12N7/00 , C12N2795/10222 , C12N2795/10243 , C12Y302/01004
摘要： The present invention provides engineered bacteriophages that express at least one biofilm degrading enzyme on their surface and uses thereof for degrading bacterial biofilms. The invention also provides genetically engineered bacteriophages expressing the biofilm degrading enzymes and proteins necessary for the phage to replicate in different naturally occurring biofilm producing bacteria. The phages of the invention allow a method of biofilm degradation by the use of one or only a few administration of the phage because the system using these phages is self perpetuating, and capable of degrading biofilm even when the concentration of bacteria within the biofilm is low.
摘要翻译：本发明提供了在其表面上表达至少一种生物膜降解酶的工程化噬菌体及其用于降解细菌生物膜的工程噬菌体。本发明还提供表达生物膜降解酶和蛋白质在不同天然存在的生物膜产生细菌中复制的噬菌体所需的遗传工程化噬菌体。本发明的噬菌体允许通过使用一种或仅少量的噬菌体施用来生物膜降解的方法，因为使用这些噬菌体的系统是自我延续的，并且即使当生物膜内的细菌浓度低时也能降解生物膜。

9. 发明授权

US08153119B2 Engineered enzymatically active bacteriophage and methods for dispersing biofilms 有权
标题翻译：工程化的酶活性噬菌体和分散生物膜的方法
公开(公告)号：US08153119B2
公开(公告)日：2012-04-10
申请号：US12337677
申请日：2008-12-18
申请人： James J Collins , Timothy Kuan-Ta Lu
发明人： James J Collins , Timothy Kuan-Ta Lu
IPC分类号： A01N63/00 , A61K38/43 , C12P21/06 , C12P21/04 , C12N15/09 , C12N15/00 , C12N1/00
CPC分类号： A01N63/02 , C12N7/00 , C12N9/2402 , C12N2795/10211 , C12N2795/10221 , C12N2795/10232 , C12Y207/07006 , C12Y302/01052
摘要： The present invention is directed to engineered enzymatically active bacteriophages that are both capable of killing the bacteria by lysis and dispersing the bacterial biofilm because they have been also engineered to express biofilm-degrading enzymes, particularly dispersin B (DspB), an enzyme that hydrolyzes β-1,6-N-acetyl-D-glucosamine, a crucial adhesion molecule needed for biofilm formation and integrity in Staphylococcus and E. coli, including E. coli K-12, as well as clinical isolates.
摘要翻译：本发明涉及工程化的酶活性噬菌体，其能够通过裂解和分散细菌生物膜来杀死细菌，因为它们也被工程化以表达生物降膜酶，特别是分解B（DspB），其是水解＆bgr的酶 ; -1,6-N-乙酰基-D-葡糖胺，生物膜形成所需的关键粘附分子和葡萄球菌和大肠杆菌（包括大肠杆菌K-12）以及临床分离物中的完整性。

10. 发明申请

US20100322903A1 ENGINEERED BACTERIOPHAGES AS ADJUVANTS FOR ANTIMICROBIAL AGENTS AND COMPOSITIONS AND METHODS OF USE THEREOF 有权
标题翻译：工程化杀菌剂作为抗菌药物及其组合物的使用方法及其使用方法
公开(公告)号：US20100322903A1
公开(公告)日：2010-12-23
申请号：US12812212
申请日：2009-01-12
申请人： James J Collins , Timothy Kuan-Ta Lu
发明人： James J Collins , Timothy Kuan-Ta Lu
IPC分类号： A61K35/76 , C12N7/01 , A61P31/04
CPC分类号： C07K14/005 , A61K35/76 , C12N15/113 , C12N2320/32 , C12N2330/30 , C12N2795/14122 , C12N2795/14132
摘要： The present invention relates to the treatment and prevention of bacteria and bacterial infections. In particular, the present invention relates to engineered bacteriophages used in combination with antimicrobial agents to potentiate the antimicrobial effect and bacterial killing by the antimicrobial agent. The present invention generally relates to methods and compositions comprising engineered bacteriophages and antimicrobial agents for the treatment of bacteria, and more particularly to bacteriophages comprising agents that inhibit antibiotic resistance genes and/or cell survival genes, and/or bacteriophages comprising repressors of SOS response genes or inhibitors of antimicrobial defense genes and/or expressing an agent which increases the sensitivity of bacteria to an antimicrobial agent in combination with at least one antimicrobial agent, and their use thereof.
摘要翻译：本发明涉及细菌和细菌感染的治疗和预防。特别地，本发明涉及与抗微生物剂组合使用的工程化噬菌体，以增强抗微生物效果和抗微生物剂的细菌杀伤作用。本发明一般涉及包含工程化噬菌体和用于治疗细菌的抗微生物剂的方法和组合物，更具体地涉及包含抑制抗生素抗性基因和/或细胞存活基因的试剂和/或包含SOS应答基因阻遏物的噬菌体的噬菌体或抗微生物防御基因的抑制剂和/或表达增加细菌对抗微生物剂与至少一种抗微生物剂的敏感性的试剂及其用途。

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