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1. 发明授权

US09697460B2 Biological analog-to-digital and digital-to-analog converters 有权
公开(公告)号：US09697460B2
公开(公告)日：2017-07-04
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： C12P21/06 , C07H21/04 , G06N3/00 , H03M1/36 , H03M1/74
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.

2. 发明授权

US09056899B2 Engineered bacteriophages as adjuvants for antimicrobial agents and compositions and methods of use thereof 有权
标题翻译：工程化噬菌体作为抗微生物剂的佐剂及其组合物及其使用方法
公开(公告)号：US09056899B2
公开(公告)日：2015-06-16
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： A01N63/00 , C12N7/01 , C07K14/005 , A61K35/76 , C12N15/113
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。

3. 发明申请

US20140178864A1 MODULAR NUCLEIC ACID-BASED CIRCUITS FOR COUNTERS, BINARY OPERATIONS, MEMORY, AND LOGIC 有权
标题翻译：用于计数器，二进制运算，存储器和逻辑的基于核酸的基于电路的电路
公开(公告)号：US20140178864A1
公开(公告)日：2014-06-26
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： C12Q1/68
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.
摘要翻译：我们已经创建了新颖的遗传算法设计及其使用方法，其利用DNA重组酶来提供称为单一转换酶存储器模块（SIMM）的模块化系统，用于对细胞和细胞系统中的存储器进行编码。通过使用> 100个已知重组酶来创建后续模块，我们的设计可以轻松扩展到高数量计算。我们设计的基因计数器设计中的灵活性是通过菊花链连接单个模块化组件（即SIMM）来提供的。设计的遗传计数器的这些模块化组件可以组合在其他网络拓扑中，以创建执行逻辑和存储器的电路。我们的新颖设计的基因计数器设计允许维持记忆，并提供通过在其同源识别位点之间表达重组酶来提供离散状态之间的计数能力。

4. 发明授权

US08645115B2 Modular nucleic acid-based circuits for counters, binary operations, memory and logic 有权
标题翻译：用于计数器，二进制操作，存储器和逻辑的基于模块化的基于核酸的电路
公开(公告)号：US08645115B2
公开(公告)日：2014-02-04
申请号：US13141165
申请日：2009-12-22
申请人： James J Collins , Timothy Lu
发明人： James J Collins , Timothy Lu
IPC分类号： G06G7/48 , G06G7/58 , G01N33/48 , G01N31/00
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.
摘要翻译：我们已经创建了新颖的遗传算法设计及其使用方法，其利用DNA重组酶来提供称为单一转换酶存储器模块（SIMM）的模块化系统，用于对细胞和细胞系统中的存储器进行编码。通过使用> 100个已知重组酶来创建后续模块，我们的设计可以轻松扩展到高数量计算。我们设计的基因计数器设计中的灵活性是通过菊花链连接单个模块化组件（即SIMM）来提供的。设计的遗传计数器的这些模块化组件可以组合在其他网络拓扑中，以创建执行逻辑和存储器的电路。我们的新颖设计的基因计数器设计允许维持记忆，并提供通过在其同源识别位点之间表达重组酶来提供离散状态之间的计数能力。

5. 发明申请

US20120244126A1 ENGINEERED ENZYMATICALLY ACTIVE BACTERIOPHAGE AND METHODS FOR DISPERSING BIOFILMS 审中-公开
标题翻译：工程化生物活性细菌和分散生物膜的方法
公开(公告)号：US20120244126A1
公开(公告)日：2012-09-27
申请号：US13412838
申请日：2012-03-06
申请人： James J. Collins , Timothy Kuan-Ta Lu
发明人： James J. Collins , Timothy Kuan-Ta Lu
IPC分类号： A01N63/02 , A01P1/00 , C12N7/01
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。

6. 发明申请

US20110119259A1 NETWORK BIOLOGY APPROACH FOR IDENTIFYING TARGETS FOR COMBINATION THERAPIES 审中-公开
标题翻译：识别组合治疗目标的网络生物学方法
公开(公告)号：US20110119259A1
公开(公告)日：2011-05-19
申请号：US12989083
申请日：2009-04-24
申请人： James J. Collins , Zheng Li , Ayla Ergun
发明人： James J. Collins , Zheng Li , Ayla Ergun
IPC分类号： G06F17/30
CPC分类号： G16B5/00
摘要： Described herein is a network biology approach useful for the identification of multiple therapeutic targets, which can be targeted simultaneously using an agent (or a plurality of agents) to modulate cellular phenotypes, or in combination with pharmaceutical compounds to improve drug sensitivity and/or reduce drug doses to maintain efficacy while minimizing side effects. The preferred approach disclosed herein relies on first identifying the mediators of a condition of interest, and second, selecting gene combinations that are in competing/parallel pathways as targets for combination therapy.
摘要翻译：本文描述了一种可用于鉴定多种治疗靶标的网络生物学方法，其可以使用试剂（或多种试剂）同时靶向调节细胞表型，或与药物化合物组合以改善药物敏感性和/或降低药物剂量以维持功效，同时尽量减少副作用。本文公开的优选方法依赖于首先鉴定感兴趣病症的介质，其次，选择以竞争/平行途径为基础的组合作为组合疗法的靶标。

7. 发明申请

US20090155215A1 ENGINEERED ENZYMATICALLY ACTIVE BACTERIOPHAGE AND METHODS FOR DISPERSING BIOFILMS 有权
标题翻译：工程化生物活性细菌和分散生物膜的方法
公开(公告)号：US20090155215A1
公开(公告)日：2009-06-18
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 , C12N7/01
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，特别是分解蛋白B（DspB），其是水解β -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。

8. 发明授权

US06841376B2 Bistable genetic toggle switch 有权
标题翻译：双稳态遗传拨动开关
公开(公告)号：US06841376B2
公开(公告)日：2005-01-11
申请号：US09872868
申请日：2001-05-01
申请人： Timothy Gardner , James J. Collins
发明人： Timothy Gardner , James J. Collins
IPC分类号： C12N1/11 , C12N1/19 , C12N15/63 , C12N1/20 , C07H21/04 , C12N15/00 , C12N15/09 , C12N15/86
CPC分类号： C12N15/635 , C12N15/63
摘要： Provided are methods and compositions for regulating gene expression in a cell. The invention provides recombinant genetic toggle switches which contain a first constitutive promoter-regulatory gene operon and a second constitutive promoter-regulatory gene operon. Expression of the regulatory gene from the first operon inhibits expression from the promoter in the second operon, and expression of the regulatory gene from the second operon inhibits expression from the promoter in the first operon. By use of the toggle switch and various switching agents it is possible to reversibly switch the expression of a gene of interest between a stable “on” state and stable “off” state or vice versa via transient exposure to a switching agent.
摘要翻译：提供用于调节细胞中基因表达的方法和组合物。本发明提供含有第一组成型启动子调控基因操纵子和第二组成型启动子调控基因操纵子的重组遗传切换开关。来自第一操纵子的调节基因的表达抑制第二操纵子中启动子的表达，并且来自第二操纵子的调节基因的表达抑制来自第一操纵子中启动子的表达。通过使用拨动开关和各种开关剂，可以通过瞬时暴露于开关剂来将感兴趣的基因的表达在稳定的“导通”状态和稳定的“断开”状态之间进行可逆的切换。

9. 发明授权

US06219578B1 Galvanic vestibular stimulation system and method 失效
标题翻译：电镀前庭刺激系统及方法
公开(公告)号：US06219578B1
公开(公告)日：2001-04-17
申请号：US09392186
申请日：1999-09-09
申请人： James J. Collins , J. Timothy Inglis
发明人： James J. Collins , J. Timothy Inglis
IPC分类号： A61N136
CPC分类号： A61N1/3655 , A61N1/36036
摘要： A system and method of altering the output of a vestibular system including providing a source of time-varying galvanic current, transcutaneously delivering time-varying galvanic current to vestibular afferents associated with the vestibular system in order to modulate firing level of the vestibular afferents, and inducing a coherent time-varying sway response that counteracts postural sway. In an alternative embodiment there is provided a galvanic vestibular stimulation system including a source which transcutaneously delivers time-varying galvanic current to vestibular afferents in order to modulate the firing level of the vestibular afferents, a monitor which monitors postural sway thereby providing indication of necessary galvanic current to be delivered. The system induces a coherent time-varying sway response that counteracts the monitored postural sway.
摘要翻译：改变前庭系统的输出的系统和方法包括提供随时间变化的电流源，经皮递送时变电流到与前庭系统相关的前庭传入，以调节前庭传入物的发射水平，以及诱导抵消姿势摇摆的相干时变摇摆反应。在替代实施例中，提供了一种电流前庭刺激系统，其包括经皮递送时变电流到前庭传入物的源，以调节前庭传入物的触发水平，监测姿势摇摆的监视器，从而提供必要的电流目前交付。该系统引起一个相干的时变摇摆反应，抵消了被监测的姿势摆动。

10. 发明授权

US5782873A Method and apparatus for improving the function of sensory cells 失效
标题翻译：用于改善感觉细胞功能的方法和装置
公开(公告)号：US5782873A
公开(公告)日：1998-07-21
申请号：US703674
申请日：1996-08-27
申请人： James J. Collins
发明人： James J. Collins
IPC分类号： A61F7/00 , A61N1/05 , A61N1/36 , A61N2/00 , A61N5/06 , A61N7/00 , A61N1/00
CPC分类号： A61N2/006 , A61F7/00 , A61N1/36003 , A61N1/36007 , A61N1/3601 , A61N1/36032 , A61N2/00 , A61N5/06 , A61N7/00
摘要： Method and system for enhancing the function of sensory cells are disclosed. The method comprises locating a sensory cell area associated with the sensory cell whose function is to be enhanced and inputting a bias signal to the sensory cell area. The apparatus comprises a signal processor for producing a bias signal and an input device for inputting the bias signal to a sensory cell area associated with a sensory cell whose function is to be enhanced. Inputting the bias signal to a sensory cell area effectively lowers the threshold of sensory cells with which the sensory cell area is associated.
摘要翻译：公开了增强感觉细胞功能的方法和系统。该方法包括定位与要增强功能的感觉细胞相关联的感觉细胞区域，并将偏置信号输入到感觉细胞区域。该装置包括用于产生偏置信号的信号处理器和用于将偏置信号输入到与要增强其功能的感觉细胞相关联的感觉细胞区域的输入装置。将偏置信号输入感觉细胞区域有效地降低与感觉细胞区域相关联的感觉细胞的阈值。

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