Enhancement of the Inhibitory Activity of oatp Antisense Oligonucleotides by Incorporation of 2'-O,4'-C-Ethylene-Bridged Nucleic Acids (ENA) without a Loss of Subtype Selectivity.

Takagi M; Morita K; Nakai D; Nakagomi R; Tokui T; Koizumi M

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Enhancement of the Inhibitory Activity of oatp Antisense Oligonucleotides by Incorporation of 2'-O,4'-C-Ethylene-Bridged Nucleic Acids (ENA) without a Loss of Subtype Selectivity.

机译：通过掺入2'-O，4'-C-乙烯桥连核酸（ENA）增强燕麦反义寡核苷酸的抑制活性，而不会损失亚型选择性。

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Antisense oligonucleotides (AONs) that specifically target the genes of rat organic anion transporting polypeptide (oatp) subtypes were selected by using antisense in vitro selection (AIVS) and a conventional gene alignment program (GAP). When we incorporated several of our original 2'-O,4'-C-ethylene-bridged nucleic acid (ENA) residues into AONs, which were designed as gapmers containing a series of 2'-deoxynucleotides in the center, at both the 3' and 5' ends, the inhibitory activity of these oatp AONs was enhanced and their inhibition was mediated by RNase H cleavage. Moreover, these ENA AONs did not lose their oatp selectivity. These strategies of using AIVS and GAP to select AONs followed by incorporation of ENA residues were effective for synthesizing oatp subtype-specific AONs.

机译：通过使用体外反义选择（AIVS）和常规基因比对程序（GAP），可以选择特异靶向大鼠有机阴离子转运多肽（oatp）亚型基因的反义寡核苷酸（AON）。当我们将几个原始的2'-O，4'-C-乙烯桥连核酸（ENA）残基整合到AON中时，这些残基被设计为中间含两个2'-脱氧核苷酸的间隙子在'和5'端，增强了这些燕麦AON的抑制活性，并通过RNase H切割介导了它们的抑制作用。此外，这些ENA AON并没有失去其燕麦选择性。这些使用AIVS和GAP选择AON，然后掺入ENA残基的策略对于合成燕麦亚型特异性AON是有效的。

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《Biochemistry》 |2004年第15期|共10页
作者
Takagi M; Morita K; Nakai D; Nakagomi R; Tokui T; Koizumi M;
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正文语种 eng
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extractable nuclear antigens; Carbon ion; Nucleic Acids; Endurance of activity; 核酸类;

机译：extractable nuclear antigens;Carbon ion;Nucleic Acids;Endurance of activity;核酸类;

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1. Enhancement of the Inhibitory Activity of oatp Antisense Oligonucleotides by Incorporation of 2'-O,4'-C-Ethylene-Bridged Nucleic Acids (ENA) without a Loss of Subtype Selectivity. [J] . Takagi M, Morita K, Nakai D, Biochemistry . 2004,第15期

机译：通过掺入2'-O，4'-C-乙烯桥连核酸（ENA）增强燕麦反义寡核苷酸的抑制活性，而不会损失亚型选择性。
2. Inhibition of VEGF mRNA by 2'-O,4'-C-ethylene-bridged nucleic acids (ENA) antisense oligonucleotides and their influence on off-target gene expressions. [J] . Morita K, Yamate K, Kurakata S, Nucleosides, nucleotides and nucleic acids . 2006,第4a6期

机译：2'-O，4'-C-亚乙基桥连核酸（ENA）反义寡核苷酸对VEGF mRNA的抑制及其对脱靶基因表达的影响。
3. Synthesis and properties of 2'-O,4'-C-Ethylene-Bridged nucleic acids (ENA) as effective antisense oligonucleotides. [J] . Morita K, Takagi M, Hasegawa C, Bioorganic and medicinal chemistry . 2003,第10期

机译：作为有效反义寡核苷酸的2'-O，4'-C-乙烯桥连核酸（ENA）的合成和性质。
4. Characterization of Antisense Oligonucleotides Comprising 2'-Deoxy-2'-Fluoro-β-D-Arabinonucleic Acid (FANA) Specificity, Potency, and Duration of Activity [C] . NICOLAY FERRARI, DENIS BERGERON, ANNA-LISA TEDESCHI, Oligonucleotide Therapeutics Society . 2006

机译：反义寡核苷酸的表征包含2'-脱氧-2'-氟-β-D-亚丙核酸（FANA）特异性，效力和活性持续时间的
5. Incorporating disulfide cross-links into oligonucleotides: A new method to conformationally restrain nucleic acids. [D] . Osborne, Scott Edward. 1996

机译：将二硫键交联引入寡核苷酸：构象限制核酸的新方法。
6. Antisense inhibition of gene expression in cells by oligonucleotides incorporating locked nucleic acids: effect of mRNA target sequence and chimera design [O] . Dwaine A. Braasch, Yinghui Liu, David R. Corey 2002

机译：包含锁定核酸的寡核苷酸对细胞中基因表达的反义抑制：mRNA靶序列和嵌合体设计的影响
7. Antisense inhibition of gene expression in cells by oligonucleotides incorporating locked nucleic acids: effect of mRNA target sequence and chimera design [O] . Braasch, Dwaine A., Liu, Yinghui, Corey, David R. 2002

机译：包含锁定核酸的寡核苷酸对细胞中基因表达的反义抑制：mRNA靶序列和嵌合体设计的影响

Enhancement of the Inhibitory Activity of oatp Antisense Oligonucleotides by Incorporation of 2'-O,4'-C-Ethylene-Bridged Nucleic Acids (ENA) without a Loss of Subtype Selectivity.

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