Elimination of Off-Target Effect by Chemical Modification of 5′-End of siRNA

Yasuo Shiohama; Ryosuke Fujita; Maika SonokawaMasaaki HisanoYojiro KotakeMarija Krstic-DemonacosConstantinos DemonacosGengo KashiwazakiTakashi KitayamaMasayuki Fujii

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Elimination of Off-Target Effect by Chemical Modification of 5′-End of siRNA

机译：Elimination of Off-Target Effect by Chemical Modification of 5′-End of siRNA

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摘要

In this study, the efficiency of RNA interference of small interfering RNAs (siRNAs) bearing 5′-O-methyl-2′-deoxythymidine (X) and 5′-amino-2′, 5′-dideoxythymidine (Z) at the 5′-end of the sense strand and the antisense strand of siRNA was investigated in HeLa cells stably expressing enhanced green fluorescent protein. The results indicated that when one strand of siRNA was modified with X or Z and the other was unmodified, the X or Z modification was predominant in the process of strand selection and the unmodified strand was selected as a guide strand. When both strands are modified with X or Z, the modified antisense strand with X or Z will be selected as a guide strand with a certain probability. The resulting mature RNA-induced silencing complex exerted reduced, but still moderate silencing activity remained. These results suggest that the modification of the sense strand with X or Z eliminates the off-target effects caused by the sense strand without affecting the silencing efficiency of the siRNA.

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《Nucleic Acid Therapeutics》 |2022年第5期|438-447|共10页
作者
Yasuo Shiohama; Ryosuke Fujita; Maika SonokawaMasaaki HisanoYojiro KotakeMarija Krstic-DemonacosConstantinos DemonacosGengo KashiwazakiTakashi KitayamaMasayuki Fujii;
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作者单位

Environmental and Biological Information Group, Tropical Biosphere Research Centre, University of the Ryukyus;

Department of Biological & Environmental Chemistry, School of Humanity Oriented Science and Technology, Kindai University;

School of Science, Engineering and Environment, University of SalfordDivision of Pharmacy and Optometry, Faculty of Biology Medicine and Health, School of Health Science, University of ManchesterDepartment of Advanced Bioscience, Faculty of Agriculture, Kindai UniversityMasayuki Fujii, PhD, Department of Biological & Environmental Chemistry, School of Humanity Oriented Science and Technology, Kindai University;

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原文格式 PDF
正文语种英语
中图分类生物化学;
关键词
5′-modified siRNA; gene silencing; strand selection; RISC activity; off-target effect;

Elimination of Off-Target Effect by Chemical Modification of 5′-End of siRNA

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