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1. 发明授权

US09388425B2 Tunable genetic switch for regulating gene expression 有权
标题翻译：用于调节基因表达的可调基因切换
公开(公告)号：US09388425B2
公开(公告)日：2016-07-12
申请号：US12446300
申请日：2007-10-19
申请人： James J Collins , Tara L Deans
发明人： James J Collins , Tara L Deans
IPC分类号： C12N15/11 , C12N15/85 , C12N15/63
CPC分类号： C12N15/85 , C12N15/111 , C12N15/63 , C12N2310/14 , C12N2320/30 , C12N2800/30 , C12N2830/005 , C12N2830/006 , C12N2830/50 , C12N2840/102
摘要： The present invention relates generally the field of genetics, in particular methods, compositions and systems for controlling the inducible expression of transgenes, while eliminating background expression of transgene expression. The present invention relates to methods of use of the compositions and systems as disclosed herein for controlling the inducible expression of transgenes while eliminating background expression of transgene expression, such as use in, for example, the in generation of transgenic animals, use in therapeutic application and use in assays. In some embodiments, the present invention relates to a system of controlled expression of RNAi molecules which target binding sites in the untranslated regions of transgene, thereby the expression of the transgene is modulated and leakiness is reduced. The compositions and methods of the present invention can be used to for therapy, prophylaxis, research and diagnostics in diseases and disorders which afflict mammalian species, generation of transgenic animals, in the study of biological processes as well as for enhance performance of agricultural crops.
摘要翻译：本发明一般涉及遗传学领域，特别是用于控制转基因诱导表达的方法，组合物和系统，同时消除转基因表达的背景表达。本发明涉及如本文所公开的用于控制转基因诱导表达同时消除转基因表达的背景表达的用途的方法，例如在例如转基因动物的产生中的用途，在治疗应用中的用途并用于测定。在一些实施方案中，本发明涉及靶向转基因非翻译区中的结合位点的RNAi分子的受控表达系统，由此调节转基因的表达并降低渗透性。本发明的组合物和方法可用于治疗，预防，研究和诊断在影响哺乳动物物种的疾病和病症中，产生转基因动物，研究生物过程以及增强农作物的性能。

2. 发明申请

US20150366889A1 PROTON-MOTIVE FORCE STIMULATION TO POTENTIATE AMINOGLYCOSIDE ANTIBIOTICS AGAINST PERSISTENT BACTERIA 有权
标题翻译：原始动力学刺激阻止氨基甲酸酯抗生素对抗细菌性细菌
公开(公告)号：US20150366889A1
公开(公告)日：2015-12-24
申请号：US14115528
申请日：2012-05-04
申请人： Mark P. Brynildsen , James J. Collins , Kyle R. Allison
发明人： Mark P. Brynildsen , James J. Collins , Kyle R. Allison
IPC分类号： A61K31/7036 , A61K31/7004 , A61K31/047
CPC分类号： A61K31/7036 , A61K9/0019 , A61K31/047 , A61K31/19 , A61K31/7004 , A61K45/06 , Y02A50/473 , A61K2300/00
摘要： Provided herein are compositions and methods to improve treatment of chronic infections, and reduce, delay, or inhibit formation of biofilms, using specific combinations of aminoglycoside antibiotics and high, localized concentrations of one or more PMF stimulating compounds. These novel methods are easily adapted to clinical settings as toxicity and efficacy of the antibiotics and metabolites used have already been studied in vivo, and as dosing for both the antibiotics and metabolites are known. These approaches and therapeutic methods are also useful with non-metabolic chemicals that induce proton-motive force in bacteria.
摘要翻译：本文提供了使用氨基糖苷类抗生素的特定组合以及一种或多种PMF刺激化合物的高定量浓度来改善慢性感染治疗并减少，延迟或抑制生物膜形成的组合物和方法。这些新颖的方法很容易适应于临床环境，因为所用的抗生素和代谢物的毒性和功效已经在体内进行了研究，并且因为抗生素和代谢物的给药都是已知的。这些方法和治疗方法对于在细菌中诱导质子运动力的非代谢化学物质也是有用的。

3. 发明授权

US08306752B1 Method to determine transcriptional regulation pathways in organisms 有权
标题翻译：确定生物体内转录调控途径的方法
公开(公告)号：US08306752B1
公开(公告)日：2012-11-06
申请号：US12271944
申请日：2008-11-17
申请人： Timothy S. Gardner , James J. Collins , Boris Hayete , Jeremiah Faith
发明人： Timothy S. Gardner , James J. Collins , Boris Hayete , Jeremiah Faith
IPC分类号： G06F7/00
CPC分类号： G06F19/24 , G06F19/20
摘要： The invention relates to computer-implemented methods and systems for identifying regulatory relationships between expressed regulating polypeptides and targets of the regulatory activities of such regulating polypeptides. More specifically, the invention provides a new method for identifying regulatory dependencies between biochemical species in a cell. In particular embodiments, provided are computer-implemented methods for identifying a regulatory interaction between a transcription factor and a gene target of the transcription factor, or between a transcription factor and a set of gene targets of the transcription factor. Further provided are genome-scale methods for predicting regulatory interactions between a set of transcription factors and a corresponding set of transcriptional target substrates thereof.
摘要翻译：本发明涉及用于鉴定表达的调节多肽与这些调节多肽的调节活性的靶标之间的调节关系的计算机实现的方法和系统。更具体地，本发明提供了用于鉴定细胞中生物化学物质之间的调节依赖性的新方法。在特定实施方案中，提供了用于鉴定转录因子与转录因子的转录因子和基因靶标之间或转录因子与转录因子的一组基因靶标之间的调节相互作用的计算机实现的方法。还提供了用于预测一组转录因子与其相应的一组转录靶标底物之间的调节相互作用的基因组大小的方法。

4. 发明授权

US5388591A Method and apparatus for analyzing the human postural control system 失效
标题翻译：人体姿态控制系统分析方法及装置
公开(公告)号：US5388591A
公开(公告)日：1995-02-14
申请号：US987715
申请日：1992-12-09
申请人： Carlo J. De Luca , James J. Collins
发明人： Carlo J. De Luca , James J. Collins
IPC分类号： A61B5/103
CPC分类号： A61B5/1036 , A61B5/4023
摘要： A method and an apparatus for analyzing the human postural control system includes computing the mean square displacement of the center of pressure beneath a subject's feet vs. the time interval. The result is plotted as a stabilogram diffusion plot. The stabilogram diffusion plot, since reproducible, provides physiologically meaningful information from which an assessment of the subject's postural control system can be made. A Brownian diffusion coefficient, which is indicative of the level of stochastic activity of the center of pressure, can be calculated from the slope of the stabilogram diffusion plot. Also, from the slope of the log-log stabilogram diffusion plot, a determination can be made as to whether the system is moving closer to or away from a state of relative equilibrium. Finally, a short term open-loop postural control scheme, which operates before a long term closed-loop feedback postural control scheme activates, can be studied from the stabilogram diffusion plot. Also, from the stabilogram diffusion plot, a determination can be made as to when the postural control system switches from open-loop control to closed-loop control.
摘要翻译：用于分析人类姿态控制系统的方法和装置包括计算受试者脚下的压力中心与时间间隔的均方位移。结果绘制为稳态扩散图。稳定的扩散图，由于可重现，提供了生理上有意义的信息，从而可以对主体的姿势控制系统进行评估。可以从稳态扩散图的斜率计算表示压力中心的随机活动水平的布朗扩散系数。此外，从对数 - 对数稳态扩散图的斜率可以确定系统是否移动更靠近或远离相对平衡状态。最后，在稳定的闭环反馈姿势控制方案激活之前运行的短期开环姿态控制方案可以从稳态扩散图进行研究。此外，从稳态扩散图可以确定姿势控制系统何时从开环控制切换到闭环控制。

5. 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.

6. 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。

7. 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。

8. 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。

9. 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。

10. 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。

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