Abstract
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
Current Topics in Medicinal Chemistry
Title: True Antisense Oligonucleotides with Modified Nucleotides Restricted in the Nconformation
Volume: 7 Issue: 7
Author(s): Makoto Koizumi
Affiliation:
Keywords: DNA oligonucleotides, bridged nucleosides, Gapmers, Duchenne muscular dystrophy, RNA polymerase II
Abstract: 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.
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Cite this article as:
Koizumi Makoto, True Antisense Oligonucleotides with Modified Nucleotides Restricted in the Nconformation, Current Topics in Medicinal Chemistry 2007; 7 (7) . https://dx.doi.org/10.2174/156802607780487768
DOI https://dx.doi.org/10.2174/156802607780487768 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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