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公开(公告)号：US20090203530A1
公开(公告)日：2009-08-13
申请号：US11916710
申请日：2006-06-07
CPC分类号： C12N15/1068 , C12N15/1062
摘要： The invention provides a method for producing polymers having a desirable property, for example, catalytic activity or binding activity, via evolutionary nucleic acid-mediated chemistry.
摘要翻译： 本发明提供了一种通过进化核酸介导化学制备具有所需性质，例如催化活性或结合活性的聚合物的方法。
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42.发明申请公开(公告)号：US20080318807A1
公开(公告)日：2008-12-25
申请号：US11917609
申请日：2006-06-16
CPC分类号： C12N15/1068
摘要： The present invention provides methods and compositions for performing multi-step nucleic acid mediated synthesis of a highly diverse collection of molecules, for example, small molecules and polymers. In the method, in at least two steps, multiple reaction intermediates and/or products are produced in the same step by different chemical reactions.
摘要翻译： 本发明提供用于进行多步骤核酸介导的高度多样化分子收集的方法和组合物，例如小分子和聚合物。 在该方法中，在至少两个步骤中，通过不同的化学反应在同一步骤中产生多个反应中间体和/或产物。
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公开(公告)号：US07223545B2
公开(公告)日：2007-05-29
申请号：US10949163
申请日：2004-09-24
申请人： David R. Liu , Zev J. Gartner , Matthew W. Kanan
发明人： David R. Liu , Zev J. Gartner , Matthew W. Kanan
CPC分类号： C12N15/1068 , C12P1/00 , C12P19/34 , C12P21/00
摘要： Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The present invention provides methods, compositions, and systems for synthesizing, selecting, amplifying, and evolving non-natural molecules based on nucleic acid templates. The sequence of a nucleic acid template is used to direct the synthesis of non-natural molecules such as unnatural polymers and small molecules. Using this method combinatorial libraries of these molecules can be prepared and screened. Upon selection of a molecule, its encoding nucleic acid template may be amplified and/or evolved to yield the same molecule or related molecules for re-screening. The inventive methods and compositions of the present invention allow for the amplification and evolution of non-natural molecules in a manner analogous to the amplification of natural biopolymer such as polynucleotides and protein.
摘要翻译： 自然会通过迭代多样化，选择和扩增进化生物分子，如蛋白质。 本发明提供了基于核酸模板合成，选择，扩增和演化非天然分子的方法，组合物和系统。 核酸模板的序列用于引导非天然分子如非天然聚合物和小分子的合成。 使用这种方法可以制备和筛选这些分子的组合文库。 在选择分子时，其编码核酸模板可以被扩增和/或进化以产生用于重新筛选的相同分子或相关分子。 本发明的本发明的方法和组合物以与天然生物聚合物如多核苷酸和蛋白质的扩增类似的方式允许非天然分子的扩增和进化。
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公开(公告)号：US08975232B2
公开(公告)日：2015-03-10
申请号：US13812431
申请日：2011-07-29
申请人： David R. Liu , Ralph E. Kleiner
发明人： David R. Liu , Ralph E. Kleiner
CPC分类号： C07K5/02 , A61K38/12 , C07K5/1016
摘要： The present invention provides macrocyclic compounds of Formula (I): pharmaceutically acceptable salts thereof; and pharmaceutical compositions thereof, wherein R1, R2, R3, R4, RE, RF, RG, RH, RI, f, g, h, n, and m are as defined herein. The present invention further provides methods of synthesizing these macrocyclic compounds, and methods of their use and treatment. Certain aspects of the present invention relate to modulation of kinase activity, and in the treatment of kinase-associated diseases or disorders.
摘要翻译： 本发明提供式（I）的大环化合物：其药学上可接受的盐; 及其药物组合物，其中R1，R2，R3，R4，RE，RF，RG，RH，RI，f，g，h，n和m如本文所定义。 本发明还提供了合成这些大环化合物的方法及其使用和处理方法。 本发明的某些方面涉及激酶活性的调节和激素相关疾病或病症的治疗。
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公开(公告)号：US20140234289A1
公开(公告)日：2014-08-21
申请号：US14234031
申请日：2012-07-22
CPC分类号： C12N9/22 , C12Q1/44 , C12Q1/68 , C12Q1/6874 , C12Q1/6802 , C12Q2521/30
摘要： Engineered nucleases (e.g., zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and others) are promising tools for genome manipulation and determining off-target cleavage sites of these enzymes is of great interest. We developed an in vitro selection method that interrogates 1011 DNA sequences for their ability to be cleaved by active, dimeric nulceases, e.g., ZFNs and TALENs. The method revealed hundreds of thousands of DNA sequences, some present in the human genome, that can be cleaved in vitro by two ZFNs, CCR5-224 and VF2468, which target the endogenous human CCR5 and VEGF-A genes, respectively. Analysis of the identified sites in cultured human cells revealed CCR5-224-induced mutagenesis at nine off-target loci. Similarly, we observed 31 off-target sites cleaved by VF2468 in cultured human cells. Our findings establish an energy compensation model of ZFN specificity in which excess binding energy contributes to off-target ZFN cleavage and suggest strategies for the improvement of future nuclease design. It was also observed that TALENs can achieve cleavage specificity similar to or higher than that observed in ZFNs.
摘要翻译： 工程化的核酸酶（例如，锌指核酸酶（ZFN），转录激活子样效应核酸酶（TALEN）等）是用于基因组操作和确定这些酶的脱靶切割位点的有希望的工具是非常有意义的。 我们开发了一种体外选择方法，其询问1011个DNA序列的活性二聚核酸酶例如ZFN和TALEN切割的能力。 该方法显示了数十万个DNA序列，一些存在于人类基因组中，可以通过分别靶向内源性人CCR5和VEGF-A基因的两个ZFNs CCR5-224和VF2468在体外切割。 在培养的人细胞中鉴定位点的分析显示在九个离靶位点上的CCR5-224诱导诱变。 类似地，我们观察到在培养的人细胞中VF2468切割的31个离靶位点。 我们的研究结果建立了ZFN特异性的能量补偿模型，其中过量结合能有助于脱靶ZFN切割，并提出改进未来核酸酶设计的策略。 还观察到TALEN可以实现与ZFN中观察到的切割特异性相似或更高的裂解特异性。
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公开(公告)号：US08206914B2
公开(公告)日：2012-06-26
申请号：US12834072
申请日：2010-07-12
申请人： David R. Liu , Zev J. Gartner , Jeffrey B. Doyon , Christopher T. Calderone , Matthew W. Kanan , Xiaoyu Li , Thomas M. Snyder , Daniel M. Rosenbaum
发明人： David R. Liu , Zev J. Gartner , Jeffrey B. Doyon , Christopher T. Calderone , Matthew W. Kanan , Xiaoyu Li , Thomas M. Snyder , Daniel M. Rosenbaum
IPC分类号： C12Q1/68
CPC分类号： C12Q1/68 , C12N15/1068
摘要： Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The power of Nature and the flexibility of organic synthesis are combined in nucleic acid-templated synthesis. The present invention provides a variety of template architectures for performing nucleic acid-templated synthesis, methods for increasing the selectivity of nucleic acid-templated reactions, methods for performing stereoselective nucleic acid-templated reactions, methods of selecting for reaction products resulting from nucleic acid-templated synthesis, and methods of identifying new chemical reactions based on nucleic acid-templated synthesis.
摘要翻译： 自然会通过迭代多样化，选择和扩增进化生物分子，如蛋白质。 自然的力量和有机合成的灵活性结合在核酸模板合成中。 本发明提供用于进行核酸模板合成的多种模板结构，用于增加核酸模板化反应的选择性的方法，用于进行立体选择性核酸模板化反应的方法，选择由核酸 - 模板合成，以及基于核酸模板合成鉴定新化学反应的方法。
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公开(公告)号：US07998904B2
公开(公告)日：2011-08-16
申请号：US11141164
申请日：2005-05-31
申请人： David R. Liu , Zev J. Gartner , Matthew W. Kanan
发明人： David R. Liu , Zev J. Gartner , Matthew W. Kanan
IPC分类号： C40B50/00 , C40B30/00 , C40B20/04 , C40B50/10 , C40B50/16 , C40B40/00 , C07H21/02 , C12Q1/68
CPC分类号： C12N15/1068 , C12P1/00 , C12P19/34 , C12P21/00
摘要： Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The present invention provides methods, compositions, and systems for synthesizing, selecting, amplifying, and evolving non-natural molecules based on nucleic acid templates. The sequence of a nucleic acid template is used to direct the synthesis of non-natural molecules such as unnatural polymers and small molecules. Using this method combinatorial libraries of these molecules can be prepared and screened. Upon selection of a molecule, its encoding nucleic acid template may be amplified and/or evolved to yield the same molecule or related molecules for re-screening. The inventive methods and compositions of the present invention allow for the amplification and evolution of non-natural molecules in a manner analogous to the amplification of natural biopolymer such as polynucleotides and protein.
摘要翻译： 自然会通过迭代多样化，选择和扩增进化生物分子，如蛋白质。 本发明提供了基于核酸模板合成，选择，扩增和演化非天然分子的方法，组合物和系统。 核酸模板的序列用于引导非天然分子如非天然聚合物和小分子的合成。 使用这种方法可以制备和筛选这些分子的组合文库。 在选择分子时，其编码核酸模板可以被扩增和/或进化以产生用于重新筛选的相同分子或相关分子。 本发明的本发明的方法和组合物以与天然生物聚合物如多核苷酸和蛋白质的扩增类似的方式允许非天然分子的扩增和进化。
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公开(公告)号：US07771935B2
公开(公告)日：2010-08-10
申请号：US10950367
申请日：2004-09-24
IPC分类号： C12Q1/68
CPC分类号： C12Q1/68 , C12N15/1068
摘要： Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The power of Nature and the flexibility of organic synthesis are combined in nucleic acid-templated synthesis. The present invention provides a variety of template architectures for performing nucleic acid-templated synthesis, methods for increasing the selectivity of nucleic acid-templated reactions, methods for performing stereoselective nucleic acid-templated reactions, methods of selecting for reaction products resulting from nucleic acid-templated synthesis, and methods of identifying new chemical reactions based on nucleic acid-templated synthesis.
摘要翻译： 自然会通过迭代多样化，选择和扩增进化生物分子，如蛋白质。 自然的力量和有机合成的灵活性结合在核酸模板合成中。 本发明提供用于进行核酸模板合成的多种模板结构，用于增加核酸模板化反应的选择性的方法，用于进行立体选择性核酸模板化反应的方法，选择由核酸 - 模板合成，以及基于核酸模板合成鉴定新化学反应的方法。
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公开(公告)号：US07678554B2
公开(公告)日：2010-03-16
申请号：US10101461
申请日：2002-03-19
申请人： David R. Liu , Joshua A. Bittker
发明人： David R. Liu , Joshua A. Bittker
CPC分类号： C12N15/1027 , C12N15/1048 , C12N15/1058
摘要： Disclosed is a method of altering a nucleic acid. The method includes fragmenting a parent nucleic acid strand to generate nucleic acid fragments. At least a subset of the fragments are ligated to generate shuffled nucleic acid strands. A selected strand is identified from the shuffled nucleic acid strands for a criterion.
摘要翻译： 公开了一种改变核酸的方法。 该方法包括将母体核酸链断裂以产生核酸片段。 连接片段的至少一个子集以产生洗牌的核酸链。 从洗牌的核酸链中鉴定出选择的链，用于标准。
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50.发明申请公开(公告)号：US20100048422A1
公开(公告)日：2010-02-25
申请号：US11989257
申请日：2006-07-21
CPC分类号： C12N15/102 , C12N15/1093 , C12N15/52
摘要： The present invention provides a method producing a modified assembly line, such as those that produce non-ribosomal peptides and polyketides. The modified assembly lines of the invention can be used to produce novel compounds with therapeutic activities. The invention also provides organisms containing modified assembly lines and libraries of modified assembly lines.
摘要翻译： 本发明提供了生产改性装配线的方法，例如产生非核糖体肽和聚酮化合物的那些方法。 本发明的改性装配线可用于生产具有治疗活性的新型化合物。 本发明还提供了包含改进的组装线的生物体和改进的装配线的文库。
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