2007
DOI: 10.2174/156802607780487768
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True Antisense Oligonucleotides with Modified Nucleotides Restricted in the Nconformation

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, … Show more

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Cited by 20 publications
(6 citation statements)
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“…We believe that the 4¢-alkoxy-2¢-deoxynucleosides will be interesting building units for assembly of the phosphodiester 4¢alkoxyoligodeoxynucleotides as new interesting RNA chimeras. 49…”
Section: Discussionmentioning
confidence: 99%
“…We believe that the 4¢-alkoxy-2¢-deoxynucleosides will be interesting building units for assembly of the phosphodiester 4¢alkoxyoligodeoxynucleotides as new interesting RNA chimeras. 49…”
Section: Discussionmentioning
confidence: 99%
“…Chemically modified antisense oligonucleotides (AOs) are powerful tools for the regulation of gene expression . AO modifications, which improve their affinity for cognate RNA by the conformational restriction of the sugar–phosphate backbone in the RNA-like C3′- endo conformation (e.g., 2′- O -Me, 2′- O -MOE, and LNA), are a powerful tool for antisense drug design, which target metabolic and cardiovascular diseases as well as cancer . In addition, progress in AO chemistry is closely related to the development of RNAi technologies and the advance of siRNAs and miRNAs from basic research to therapeutic applications …”
mentioning
confidence: 99%
“…Oligonucleotides modified with nucleotides restricted in the N-conformation form stable duplexes with RNA (Koizumi, 2007). Such oligonucleotides, modified with, e.g., 2 -O-Me, 2 -O-MOE, and LNA (Manoharan, 1999;Kaur et al, 2007;Veedu and Wengel, 2010), have been employed in antisense drug design targeting metabolic and cardiovascular diseases and cancer (Prakash and Bhat, 2007;Prakash, 2011).…”
Section: Background Informationmentioning
confidence: 99%