Loss of silencing activity caused by 5＇-terminal modification with D-/L-isonucleotide （isoNA） or locked nucleic acid （LNA） could not be restored by 5＇-terminal phosphorylation

In this study, a series of 5＇-phosphorylated siRNAs with D-/L-isonucleotide （isoNA） or locked nucleic acid （LNA） incorporated at the 5＇-terminus were synthesized. It was found that after incorporating either isoNA or LNA at the 5＇-terminus of the anti sense strand or sense strand, the silencing acti...

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Published in中国科学：化学英文版 no. 2; pp. 329 - 334
Main Author HUANG Ye CHEN Zhuo WANG Zhuo LI YaTing CHEN Yue YANG ZhenJun ZHANG Lille
Format Journal Article
LanguageEnglish
Published 2014
Subjects
LNA
siRNA
修饰
损失
活性
磷酸化
还原
锁核酸
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Summary:In this study, a series of 5＇-phosphorylated siRNAs with D-/L-isonucleotide （isoNA） or locked nucleic acid （LNA） incorporated at the 5＇-terminus were synthesized. It was found that after incorporating either isoNA or LNA at the 5＇-terminus of the anti sense strand or sense strand, the silencing activity of modified strands has been inhibited, which cannot be recovered by phos- phorylation at the 5＇-terminus; however, the silencing activity of unmodified strand to its own target was increased. This work indicates that the isoNA and LNA modification at 5＇-terminus can interfere with the strand selection during the RISC assem- bling process, and the disturbance of the 5＇-phosporylation should not be the only viable mechanism.
Bibliography:isonucleotide, locked nucleic acid （LNA）, 5＇-terminal phosphorylation
In this study, a series of 5＇-phosphorylated siRNAs with D-/L-isonucleotide （isoNA） or locked nucleic acid （LNA） incorporated at the 5＇-terminus were synthesized. It was found that after incorporating either isoNA or LNA at the 5＇-terminus of the anti sense strand or sense strand, the silencing activity of modified strands has been inhibited, which cannot be recovered by phos- phorylation at the 5＇-terminus; however, the silencing activity of unmodified strand to its own target was increased. This work indicates that the isoNA and LNA modification at 5＇-terminus can interfere with the strand selection during the RISC assem- bling process, and the disturbance of the 5＇-phosporylation should not be the only viable mechanism.
11-5839/O6
ISSN:1674-7291
1869-1870