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    • 11. 发明申请
    • NUCLEIC ACID LIGANDS WITH INTRAMOLECULAR DUPLEXES
    • 具有内分泌双倍体的核酸配体
    • WO2003014369A1
    • 2003-02-20
    • PCT/US2002/027085
    • 2002-08-08
    • SOMALOGIC, INC.GOLD, LarryBRODY, Edward, N.
    • GOLD, LarryBRODY, Edward, N.
    • C12P1/68
    • C12N15/1048C12Q1/6811C40B40/00C12Q2541/101
    • The present invention provides methods and reagents for obtaining nucleic acid ligands by the SELEX process. In particular, the present invention provides methods and reagents for obtaining nucleic acid ligands of general composition 5' A-L-AI 31, wherein L forms the target-binding region of the nucleic acid ligand, and wherein sequence A is complementary in sequence to sequence A', such that A and A' are capable of forming an intramolecular duplex. The nucleic acid ligands of the invention are obtained by performing the SELEX process or the photoSELEX process using a candidate mixture of nucleic acids, each nucleic acid in the candidate mixture comprising the sequence 51 A-R-A' 3', wherein R is a region of at least partially-randomized sequence.
    • 本发明提供了通过SELEX方法获得核酸配体的方法和试剂。 特别地,本发明提供用于获得通用组合物5'AL-AI31的核酸配体的方法和试剂,其中L形成核酸配体的靶结合区,其中序列A与序列A的序列互补 ',使得A和A'能够形成分子内的双链体。 本发明的核酸配体通过使用核酸的候选混合物进行SELEX方法或光猝灭过程获得,候选混合物中的每个核酸包含序列51ARA'3',其中R是至少一个区域 部分随机序列。
    • 12. 发明申请
    • METHOD AND APPARATUS FOR THE AUTOMATED GENERATION OF NUCLEIC ACID LIGANDS
    • 用于自动生成核酸配体的方法和装置
    • WO2002077262A2
    • 2002-10-03
    • PCT/US2002/008766
    • 2002-03-21
    • SOMALOGIC, INC.
    • GOLD, LarryZICHI, Dominic, A.SMITH, Jonathan, DrewSCHNEIDER, Daniel, J.
    • C12Q
    • C12N15/1048
    • The present invention includes a method and device for performing the automated SELEX process, including automated photoSELEX process embodiments, and automated affinity SELEX process embodiments. The automated photoSELEX embodiments included an embodiment wherein target protein and nucleic acid ligands are photocrosslinked in solution. The steps of the SELEX process are performed at one or more work stations on a work surface by a robotic manipulator controlled by a computer. Also included in the invention are photocrosslinking nucleic acid ligands to human neutrophil elastase (hNE), HIV-1 MN gp120, human L-selectin, human P-Selectin, human platelet-derived growth factor (PDGF), human alpha-thrombin, human basic fibroblast growth factor (bFGF), HIV-1 MN gp120, Angiogenin, Interleukin-4, β-Nerve Growth Factor (β-NGF), Transforming Growth Factor β1, Interleukin-7, Kininogen, Plasmin, Serum Amyloid P, Thrombopoietin (Tpo), Coagulation Factor IX, Coagulation Factor XII, Endostatin, Factor H, Collagen, Cytotoxic T lymphocyte-associated protein-4 Fc (CTLA-4 Fc), Hepatocyte Growth Factor (HGF), Insulin-like growth factor binding protein-3 (IGFBP-3), UDP-glucuronosyl transferase (UGT) 1A1, UGT 1A10, and UGT 1A3.
    • 本发明包括用于执行自动化SELEX过程的方法和装置,包括自动化photoSELEX过程实施例和自动化亲和性SELEX过程实施例。 自动化的photoSELEX实施方案包括其中靶蛋白和核酸配体在溶液中光交联的实施方案。 SELEX过程的步骤由工作表面上的一个或多个工作站由计算机控制的机器人操纵器执行。 本发明还包括与人嗜中性粒细胞弹性蛋白酶(hNE),HIV-1MN gp120,人L-选择蛋白,人P-选择蛋白,人血小板衍生生长因子(PDGF),人α-凝血酶,人类基础的光交联核酸配体 成纤维细胞生长因子(bFGF),HIV-1MN gp120,血管生成素,白介素-4,β神经生长因子(β-NGF),转化生长因子β1,白介素-7,促肾上腺素,血浆素,血清淀粉样蛋白P,血小板生成素 ),凝血因子IX,凝血因子XII,内皮抑素,因子H,胶原蛋白,细胞毒性T淋巴细胞相关蛋白-4 Fc(CTLA-4FC),肝细胞生长因子(HGF),胰岛素样生长因子结合蛋白-3( IGFBP-3),UDP-葡糖醛酸基转移酶(UGT)1A1,UGT 1A10和UGT 1A3。
    • 16. 发明申请
    • METHODS AND REAGENTS FOR DETECTING TARGET BINDING BY NUCLEIC ACID LIGANDS
    • 通过核酸配体检测目标结合的方法和试剂
    • WO2003070984A1
    • 2003-08-28
    • PCT/US2003/004142
    • 2003-02-10
    • SOMALOGIC, INC.GOLD, LarryZICHI, Dominic, A.SMITH, Jonathan, DrewSCHNEIDER, Daniel, J.GREEF, Chad
    • GOLD, LarryZICHI, Dominic, A.SMITH, Jonathan, DrewSCHNEIDER, Daniel, J.GREEF, Chad
    • C12Q1/68
    • C12N15/115G01N33/58
    • The present invention provides novel methods and reagents for detecting the binding of protein targets to nucleic acid ligands. Using Universal Protein Stains (UPS), proteins bound by nucleic acid ligands may be labeled with a detectable moiety. The methods and reagents are particularly useful for the detection of protein targets bound to multiplexed arrays of nucleic acid ligands. The present invention also provides novel methods for the multiplexed evaluation of photocrosslinking nucleic acid ligands. The methods allow one simultaneously to: (1) evaluate the performance (dynamic range) of a plurality of photocrosslinking nucleic acid ligands; and (2) assess the specificity of each photocrosslinking nucleic acid ligand for its cognate target protein. Photocrosslinking nucleic acid ligands with the most desirable properties can then be selected for use in diagnostic and prognostic medical assays. The present invention also provides a photocrosslinking nucleic acid ligand that binds specifically to HIV gp120MN.
    • 本发明提供用于检测蛋白质靶标与核酸配体的结合的新型方法和试剂。 使用通用蛋白污渍(UPS),可以用可检测的部分标记由核酸配体结合的蛋白质。 所述方法和试剂对于检测与核酸配体复合阵列结合的蛋白质靶标特别有用。 本发明还提供了用于光交联核酸配体的多重评价的新方法。 该方法同时允许:(1)评估多个光交联核酸配体的性能(动态范围); 和(2)评估每个光交联核酸配体对其同源靶蛋白的特异性。 然后可以选择具有最理想特性的光交联核酸配体用于诊断和预后医学测定。 本发明还提供了与HIV gp120MN特异性结合的光交联核酸配体。