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1. 发明申请

WO2008051854A3 A TUNABLE GENETIC SWITCH FOR REGULATING GENE EXPRESSION 审中-公开
标题翻译：一个可调控的基因表达调控基因表达系统
公开(公告)号：WO2008051854A3
公开(公告)日：2008-07-31
申请号：PCT/US2007081965
申请日：2007-10-19
申请人： UNIV BOSTON , COLLINS JAMES J , DEANS TARA L
发明人： COLLINS JAMES J , DEANS TARA L
IPC分类号： C12N15/63 , C12N15/85
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同时消除转基因表达的背景表达的遗传学领域，尤其是方法，组合物和系统。本发明涉及使用本文公开的组合物和系统来控制转基因的可诱导表达，同时消除转基因表达的背景表达，例如用于转基因动物的产生，用于治疗应用并用于分析。在一些实施方案中，本发明涉及靶向RNAi分子的受控表达的系统，其靶向转基因的非翻译区中的结合位点，由此调节转基因的表达并降低泄漏。本发明的组合物和方法可用于治疗，预防，研究和诊断折磨哺乳动物物种的疾病和病症，生成转基因动物，研究生物过程以及提高农作物的性能。

2. 发明申请

WO2008051854A9 A TUNABLE GENETIC SWITCH FOR REGULATING GENE EXPRESSION 审中-公开
标题翻译：用于调节基因表达的基因遗传开关
公开(公告)号：WO2008051854A9
公开(公告)日：2008-06-19
申请号：PCT/US2007081965
申请日：2007-10-19
申请人： UNIV BOSTON , COLLINS JAMES J , DEANS TARA L
发明人： COLLINS JAMES J , DEANS TARA L
IPC分类号： C12N15/09
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。

3. 发明申请

WO2006137847A2 ENGINEERED ENZYMATICALLY ACTIVE BACTERIOPHAGES AND METHODS OF USES THEREOF 审中-公开
标题翻译：工程化生物活性物质及其使用方法
公开(公告)号：WO2006137847A2
公开(公告)日：2006-12-28
申请号：PCT/US2005032365
申请日：2005-09-12
申请人： UNIV BOSTON , MASSACHUSETTS INST TECHNOLOGY , COLLINS JAMES J , KOBAYASHI HIDEKI , KEARN MADS , ARAKI MICHIHIRO , FRIEDLAND ARI , KUAN-TA LU TIMOTHY
发明人： COLLINS JAMES J , KOBAYASHI HIDEKI , KEARN MADS , ARAKI MICHIHIRO , FRIEDLAND ARI , KUAN-TA LU TIMOTHY
IPC分类号： 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。

4. 发明申请

WO2010141135A3 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：WO2010141135A3
公开(公告)日：2014-04-03
申请号：PCT/US2010026357
申请日：2010-03-05
申请人： UNIV BOSTON , MASSACHUSETTS INST TECHNOLOGY , COLLINS JAMES J , KOERIS MICHAEL , LU TIMOTHY KUAN-TA , CHAU TANGUY MY , STEPHANOPOULOS GREGORY
发明人： COLLINS JAMES J , KOERIS MICHAEL , LU TIMOTHY KUAN-TA , CHAU TANGUY MY , STEPHANOPOULOS GREGORY
IPC分类号： C12P21/06 , C07H21/04
CPC分类号： C12N7/00 , A61K35/76 , A61K38/1767 , C07K14/43504 , C07K14/43563 , C07K14/463 , C12N9/503 , C12N2795/10221 , C12N2795/10231 , C12N2795/10232 , C12N2795/12032 , C12N2795/12043 , C12N2795/14132 , C12N2795/14143
摘要： The present invention is generally related to engineered bacteriophages expressing antimicrobial peptides or lytic enymes or fragments thereof for targeting a broad spectum 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抗微生物肽或溶解酶或其片段的工程化噬菌体，用于靶向细菌宿主的宽谱，以及用于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。

5. 发明申请

WO2012151474A3 PROTON-MOTIVE FORCE STIMULATION TO POTENTIATE AMINOGLYCOSIDE ANTIBIOTICS AGAINST PERSISTENT BACTERIA 审中-公开
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：WO2012151474A3
公开(公告)日：2013-01-10
申请号：PCT/US2012036492
申请日：2012-05-04
申请人： UNIV BOSTON , COLLINS JAMES J , ALLISON KYLE R , BRYNILDSEN MARK P
发明人： COLLINS JAMES J , ALLISON KYLE R , BRYNILDSEN MARK P
IPC分类号： A61K31/00 , A61K31/7036 , A61P31/00
CPC分类号： A61K31/7036 , A61K9/0019 , A61K31/047 , A61K31/19 , A61K31/7004 , A61K45/06 , 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。

6. 发明申请

WO2011066541A3 BIOLOGICAL CIRCUIT CHEMOTACTIC CONVERTERS 审中-公开
标题翻译：生物电路化学转换器
公开(公告)号：WO2011066541A3
公开(公告)日：2011-10-20
申请号：PCT/US2010058341
申请日：2010-11-30
申请人： UNIV BOSTON , MASSACHUSETTS INST TECHNOLOGY , COLLINS JAMES J , LU TIMOTHY KUAN-TA
发明人： COLLINS JAMES J , LU TIMOTHY KUAN-TA
IPC分类号： C12N15/09 , C12N15/63 , C12Q1/02 , C12Q1/68
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。

7. 发明申请

WO2009137136A3 IN VIVO GENE SENSORS 审中-公开
标题翻译： VIVO基因传感器
公开(公告)号：WO2009137136A3
公开(公告)日：2013-03-21
申请号：PCT/US2009034296
申请日：2009-02-17
申请人： UNIV BOSTON , MASSACHUSETTS INST TECHNOLOGY , COLLINS JAMES J , LU TIMOTHY KUAN-TA
发明人： COLLINS JAMES J , LU TIMOTHY KUAN-TA
IPC分类号： A61K48/00 , C12N15/10 , C12N15/11 , C12N15/62 , C12N15/63
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. 发明申请

WO2009137136A9 IN VIVO GENE SENSORS 审中-公开
标题翻译：体内基因传感器
公开(公告)号：WO2009137136A9
公开(公告)日：2009-12-30
申请号：PCT/US2009034296
申请日：2009-02-17
申请人： UNIV BOSTON , MASSACHUSETTS INST TECHNOLOGY , COLLINS JAMES J , LU TIMOTHY KUAN-TA
发明人： COLLINS JAMES J , LU TIMOTHY KUAN-TA
IPC分类号： C12Q1/68
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的核酸传感器 - 效应基因电路。在没有靶基因的细胞中，电路抑制例如效应物产生，但是在靶基因存在下抑制受到竞争，使得合成传感器解除抑制并允许效应子基因表达。所描述的方法和组合物还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治疗或消除。在某些方面，所述的方法和组合物允许在生物体中特定靶向的细胞群中选择性表达诸如治疗性基因产物的试剂。

9. 发明申请

WO2007136787A2 METHOD TO DETERMINE TRANSCRIPTIONAL REGULATION PATHWAYS IN ORGANISMS 审中-公开
标题翻译：确定有机体内转录调控途径的方法
公开(公告)号：WO2007136787A2
公开(公告)日：2007-11-29
申请号：PCT/US2007011966
申请日：2007-05-17
申请人： UNIV BOSTON , GARDNER TIMOTHY S , COLLINS JAMES J , HAYETE BORIS , FAITH JEREMIAH
发明人： GARDNER TIMOTHY S , COLLINS JAMES J , HAYETE BORIS , FAITH JEREMIAH
IPC分类号： G06F19/20 , G06F19/24
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控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规模的方法。

10. 发明申请

WO2004046321A3 CIS/TRANS RIBOREGULATORS 审中-公开
标题翻译： CIS / TRANS RIBOREGULATORS
公开(公告)号：WO2004046321A3
公开(公告)日：2005-02-03
申请号：PCT/US0336506
申请日：2003-11-14
申请人： UNIV BOSTON , COLLINS JAMES J , ISAACS FARREN J , DWYER DANIEL J , CANTOR CHARLES R
发明人： COLLINS JAMES J , ISAACS FARREN J , DWYER DANIEL J , CANTOR CHARLES R
IPC分类号： C12N15/11 , C12N15/67 , C12Q1/68 , C07H21/04 , A01K67/00
CPC分类号： C12N15/67 , C12N15/11 , C12N2310/53 , C12Q1/6897
摘要： The present invention provides nucleic acid molecules, DNA constructs, plasmids, and methods for post-transcriptional regulation of gene expression using RNA molecules to both repress and activate translation of an open reading frame. Repression of gene expression is achieved through the presence of a regulatory nucleic acid element (the cis-repressive RNA or crRNA) within the 5' untranslated region (5' UTR) of an mRNA molecule. The nucleic acid element forms a hairpin (stem/loop) structure through complementary base pairing. The hairpin blocks access to the mRNA transcript by the ribosome, thereby preventing translation. In particular, in embodiments of the invention designed to operate in prokaryotic cells, the stem of the hairpin secondary structure sequesters the ribosome binding site (RBS). In embodiments of the invention designed to operate in eukaryotic cells, the stem of the hairpin is positioned upstream of the start codon, anywhere within the 5' UTR of an mRNA. A small RNA (trans-activating RNA, or taRNA), expressed in trans, interacts with the crRNA and alters the hairpin structure. This alteration allows the ribosome to gain access to the region of the transcript upstream of the start codon, thereby activating transcription from its previously repressed state.
摘要翻译：本发明提供核酸分子，DNA构建体，质粒和用于转录后调节基因表达的方法，其使用RNA分子抑制和激活开放阅读框的翻译。通过在mRNA分子的5'非翻译区（5'UTR）内存在调节性核酸元件（顺式抑制性RNA或crRNA）来实现基因表达的抑制。核酸元件通过互补碱基配对形成发夹（茎/环）结构。发夹阻止核糖体进入mRNA转录物，从而阻止翻译。特别地，在设计用于在原核细胞中操作的本发明的实施方案中，发夹二级结构的茎螯合核糖体结合位点（RBS）。在设计用于在真核细胞中操作的本发明的实施方案中，发夹的茎位于起始密码子的上游，位于mRNA的5'UTR内的任何位置。以反式表达的小RNA（反式激活RNA或taRNA）与crRNA相互作用并改变发夹结构。这种改变允许核糖体进入起始密码子上游的转录物区域，从而从其先前的抑制状态激活转录。

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