True Antisense Oligonucleotides with Modified Nucleotides Restricted in the Nconformation

Author(s): Makoto Koizumi

Journal Name: Current Topics in Medicinal Chemistry

Volume 7 , Issue 7 , 2007

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As first-generation antisense oligonucleotides, more than a dozen phosphorothioate oligodeoxynucleotides (PS ODNs) have been clinically developed, but only one has reached the market. To improve the drawbacks of PS ODNs, such as low affinity to target mRNA and non-specific binding to proteins, modified oligonucleotides with 2-modified sugars such as 2-O-(2-methoxy)ethyl and 2-F modification or with bridged sugars such as oxyalkylene linkages between 2-oxygen and 4-carbon, have been synthesized as 2-MOE, 2-F RNA, 2,4-BNA/LNA and ENA oligonucleotides. They have shown properties of higher affinity to complementary single-stranded RNA and DNA than those of PS ODNs due to their preorganized N-conformation. On the basis of the properties of these newly designed oligonucleotides, their in vitro and in vivo applications for gene silencing as true antisense oligonucleotides have been reported. In this review, antisense applications with these modified oligonucleotides are focused on.

Keywords: DNA oligonucleotides, bridged nucleosides, Gapmers, Duchenne muscular dystrophy, RNA polymerase II

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Article Details

Year: 2007
Page: [661 - 665]
Pages: 5
DOI: 10.2174/156802607780487768
Price: $65

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