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    Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation
    4.
    发明申请
    Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation 审中-公开
    识别通过寡核苷酸调节的遗传靶标和产生用于基因调控的寡核苷酸

    公开(公告)号：US20060069518A1

    公开(公告)日：2006-03-30

    申请号：US11226882

    申请日：2005-09-14

    申请人： Lex Cowsert ,  Brenda Baker ,  John McNeil ,  Susan Freier ,  Henri Sasmor ,  Douglas Brooks ,  Cara Ohashi ,  Jacqueline Wyatt ,  Alexander Borchers ,  Timothy Vickers

    发明人： Lex Cowsert ,  Brenda Baker ,  John McNeil ,  Susan Freier ,  Henri Sasmor ,  Douglas Brooks ,  Cara Ohashi ,  Jacqueline Wyatt ,  Alexander Borchers ,  Timothy Vickers

    IPC分类号： C40B30/02

    CPC分类号： C12Q1/6811 ,  B01J2219/007 ,  C12N15/1048 ,  G16B20/00 ,  G16B30/00 ,  G16B35/00 ,  G16C20/60

    摘要： Interative, preferably computer based iterative processes for generating synthetic compounds with desired physical, chemical and/or bioactive properties, i.e., active compounds, are provided. During iterations of the processes, a target nucleic acid sequence is provided or selected, and a library of candidate nucleobase sequences is generated in silico according to defined criteria. A “virtual” oligonucleotide chemistry is chosen and a library of virtual oligonucleotide compounds having the selected nucleobase sequences is generated. These virtual compounds are reviewed and compounds predicted to have particular properties are selected. The selected compounds are robotically synthesized and are preferably robotically assayed for a desired physical, chemical or biological activity. Active compounds are thus generated and, at the same time, preferred sequences and regions of the target nucleic acid that are amenable to oligonucleotide or sequence-based modulation are identified.

    摘要翻译： 提供了用于产生具有期望的物理，化学和/或生物活性的合成化合物（即活性化合物）的相互优选的基于计算机的迭代方法。 在该过程的迭代过程中，提供或选择靶核酸序列，并且根据确定的标准以计算机生成候选核碱基序列的文库。 选择“虚拟”寡核苷酸化学，并产生具有选定的核碱基序列的虚拟寡核苷酸化合物文库。 审查这些虚拟化合物，并选择预测具有特定性质的化合物。 所选择的化合物是机械合成的，并且优选机械地测定所需的物理，化学或生物活性。 因此产生活性化合物，并且同时确定适用于寡核苷酸或基于序列的调节的靶核酸的优选序列和区域。

    METHODS OF DETERMINING POTENCY OF CHEMICALLY-SYNTHESIZED OLIGONUCLEOTIDES
    8.
    发明申请
    METHODS OF DETERMINING POTENCY OF CHEMICALLY-SYNTHESIZED OLIGONUCLEOTIDES 有权
    确定化学合成寡核苷酸的方法

    公开(公告)号：US20100267149A1

    公开(公告)日：2010-10-21

    申请号：US12445854

    申请日：2007-10-18

    申请人： Walter F. Lima ,  Timothy Vickers ,  Stanley T. Crooke

    发明人： Walter F. Lima ,  Timothy Vickers ,  Stanley T. Crooke

    IPC分类号： G01N33/53

    CPC分类号： C12Q1/6876 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2320/10 ,  Y10T436/143333

    摘要： Provided herein are methods for determining potency of RNAi agents. Such methods include, but are not limited to, cell-based and cell-free assays that measure binding of an RNAi agent with Ago2 or that measure Ago2 activity in the presence of such RNAi agents. Also provided are assays that determine potency of RNAi agents by assessing their ability to compete with other RNAi agents, including control RNAi agents, for binding and/or activation of Ago2.

    摘要翻译： 本文提供了确定RNAi剂效力的方法。 这样的方法包括但不限于测量RNAi剂与Ago2的结合或在这种RNAi剂存在下测量Ago2活性的基于细胞和无细胞的测定。 还提供了通过评估其与其他RNAi试剂（包括对照RNAi试剂）竞争与Ago2结合和/或激活的能力来测定RNAi试剂的效力的测定法。

    EFFICIENT REDUCTION OF TARGET RNA'S BY SINGLE- AND DOUBLE-STRANDED OLIGOMERIC COMPOUNDS
    9.
    发明申请
    EFFICIENT REDUCTION OF TARGET RNA'S BY SINGLE- AND DOUBLE-STRANDED OLIGOMERIC COMPOUNDS 审中-公开
    单链和双链寡聚化合物有效减少目标RNA

    公开(公告)号：US20100041047A1

    公开(公告)日：2010-02-18

    申请号：US12511437

    申请日：2009-07-29

    申请人： Timothy Vickers ,  Seongjoon Koo ,  C. Frank Bennett ,  Stanley T. Crooke ,  Nicholas M. Dean ,  Brenda F. Baker

    发明人： Timothy Vickers ,  Seongjoon Koo ,  C. Frank Bennett ,  Stanley T. Crooke ,  Nicholas M. Dean ,  Brenda F. Baker

    IPC分类号： C12Q1/68 ,  C07H21/02

    CPC分类号： C12N15/1138 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/53 ,  C12N2310/3525

    摘要： The present invention provides, inter alia, methods of selecting a single-stranded oligomeric compounds for inhibiting RNA expression, methods of generating double-stranded oligomeric compounds, methods of identifying optimized double-stranded oligomeric compounds, methods of selecting optimized single-stranded oligomeric compounds, methods of selecting optimized double-stranded oligomeric compounds, methods of identifying multifunctional oligomeric compounds, methods for optimizing target region selection for modulation of RNA expression, methods of optimizing expression modulation of RNA, and the like. The present invention further provides oligomeric compounds, 8-80 nucleobases in length targeted to a target RNA, wherein said oligomeric compound hybridizes to said target RNA and inhibits RNA levels by at least 50% in both single-stranded and double-stranded forms, and multifunctional oligomeric compounds.

    摘要翻译： 本发明尤其提供了选择用于抑制RNA表达的单链寡聚化合物的方法，产生双链寡聚化合物的方法，鉴定优化的双链寡聚化合物的方法，选择优化的单链寡聚化合物的方法 选择优化的双链寡聚化合物的方法，鉴定多功能寡聚化合物的方法，用于优化用于调节RNA表达的靶区选择的方法，优化RNA表达调节的方法等。 本发明进一步提供低聚化合物，长度靶向靶RNA的8-80个核碱基，其中所述寡聚化合物与所述靶RNA杂交并且以单链和双链形式抑制至少50％的RNA水平，以及 多官能寡聚化合物。