A specificity comparison of four antisense types: Morpholino, 2'-O-methyl RNA, DNA, and phosphorothioate DNA

A specificity comparison of four antisense types: Morpholino, 2'-O-methyl RNA, DNA, and phosphorothioate DNA
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DOI:
10.1089/oli.1.1997.7.151
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发表时间:
1997-06-01
期刊:
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
影响因子:
--
通讯作者:
Summerton, J
Summerton, J
中科院分区:
其他
文献类型:
--
作者:
Stein, D;Foster, E;Summerton, J

文献摘要

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进行无细胞翻译研究以比较四种反义结构类型的功效和特异性:DNA、硫代磷酸DNA(S-DNA)、2 ′-O-甲基RNA和吗啉代寡核苷酸,一种新的反义结构类型。在这些研究中,对每种结构类型的两个20-mer评估翻译抑制,其中一个20-mer与其在兔α-珠蛋白mRNA中的靶序列互补而另一个20-mer含有与该相同靶序列的三个错配,结果表明,在低浓度的反义寡聚体(50 nM)下,所有四种类型都提供了高特异性,但吗啉代寡聚体和2 '-O-甲基RNA提供了更好的效力。(3.5 μ M)时,所有四种类型都提供高效力,但吗啉代寡核苷酸和2 ′-O-甲基RNA提供比DNA和S-DNA显著更好的特异性。
Cell-free translation studies were carried out to compare the efficacy and specificity of four antisense structural types: DNA, phosphorothioate DNA (S-DNA), 2'-O-methyl RNA, and Morpholino oligos, a novel antisense structural type, In these studies, translational inhibition was assessed for two 20-mers of each structural type, where one 20-mer was complementary to its target sequence in rabbit alpha-globin mRNA and the other 20-mer contained three mispairs to that same target sequence, It is shown that at low concentration of antisense oligomer (50 nM) all four types provide high specificity, but the Morpholino oligos and 2'-O-methyl RNA afford better efficacy, At high oligomer concentration (3.5 mu M), all four types provide high efficacy, but the Morpholino oligos and 2'-O-methyl RNA provide substantially better specificity than the DNA and S-DNA.