Inhibition of VEGF mRNA by 2'-O,4'-C-ethylene-bridged nucleic acids (ENA) antisense oligonucleotides and their influence on off-target gene expressions.

Morita K; Yamate K; Kurakata S; Abe K; Watanabe K; Koizumi M; Imanishi T

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Inhibition of VEGF mRNA by 2'-O,4'-C-ethylene-bridged nucleic acids (ENA) antisense oligonucleotides and their influence on off-target gene expressions.

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。

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We investigated 2'-O,4'-C-ethylene-bridged nucleic acids (ENA) antisense oligonucleotides (AONs) for vascular endothelial growth factor (VEGF) in human lung carcinoma A549 cells. An ENA/DNA gapmer AON with RNase H-mediated activity was virtually stable in rat plasma and exhibited more than 90% inhibition of VEGF mRNA production. Moreover, 22 genes that are likely to bind to the AON were found in the GenBank database by BLAST and CLUSTAL W searches. Three of these genes were actually inhibited by the ENA AON. In shorter ENA AONs with fewer matched sequences of these genes, inhibitiory activities were decreased and off-target effects were improved. These results indicate that ENA AONs act in a sequence-specific manner and could be used as effective antisense drugs.

机译：我们调查了人类肺癌A549细胞中血管内皮生长因子（VEGF）的2'-O，4'-C-乙烯桥核酸（ENA）反义寡核苷酸（AON）。具有RNase H介导活性的ENA / DNA gapmer AON在大鼠血浆中几乎稳定，对VEGF mRNA产生的抑制作用超过90％。此外，通过BLAST和CLUSTAL W搜索在GenBank数据库中发现了22种可能与AON结合的基因。这些基因中的三个实际上被ENA AON抑制。在较短的ENA AON中，这些基因的匹配序列较少，抑制活性降低，脱靶效应得到改善。这些结果表明ENA AON以序列特异性方式起作用，可以用作有效的反义药物。

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《Nucleosides, nucleotides and nucleic acids》 |2006年第6期|共19页
作者
Morita K; Yamate K; Kurakata S; Abe K; Watanabe K; Koizumi M; Imanishi T;
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正文语种 eng
中图分类基础医学;
关键词
extractable nuclear antigens; bevacizumab; Carbon ion; RNA; Messenger; RNA; 信使;

机译：extractable nuclear antigens;bevacizumab;Carbon ion;RNA;Messenger;RNA;信使;

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1. VEGF硫代反义寡核苷酸抑制U937细胞VEGF的表达 [J] . 何晓燕, 童允洁, 张敏中德临床肿瘤学杂志（英文版） . 2006,第006期
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. Stunning pharmacological properties of DS-5141b, an antisense oligonucleotide consisting of 2 '-O,4 '-C-ethylene-bridged nucleic acids and 2 '-O-methyl RNA, on dystrophin mRNA exon skipping [J] . Takaishi K., Kakuta M., Ito K., Neuromuscular disorders: NMD . 2017,第Suppla2期

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4. Enhancement of the Inhibitory Activity of oatp Antisense Oligonucleotides by Incorporation of 2'-(9,4'-C-Ethylene-Bridged Nucleic Acids (ENA)without a Loss of Subtype Selectivity [J] . Miho Takagi, Koji Morita, Daisuke Nakai, Biochemistry . 2004,第14期

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6. Inhibition of the CmeABC Efflux Pump by Antisense Peptide Nucleic Acids Reduces the Emergence of Spontaneous Fluoroquinolone Resistant Mutants in Campylobacter jejuni [D] . ?Singh, Kritika 2020

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7. 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

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Inhibition of VEGF mRNA by 2'-O,4'-C-ethylene-bridged nucleic acids (ENA) antisense oligonucleotides and their influence on off-target gene expressions.

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