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

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

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  • NSTL
  • Mary Ann Liebert, Inc
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.

5′-modified siRNAgene silencingstrand selectionRISC activityoff-target effect

Yasuo Shiohama、Ryosuke Fujita、Maika Sonokawa、Masaaki Hisano、Yojiro Kotake、Marija Krstic-Demonacos、Constantinos Demonacos、Gengo Kashiwazaki、Takashi Kitayama、Masayuki Fujii

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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 Salford

Division of Pharmacy and Optometry, Faculty of Biology Medicine and Health, School of Health Science, University of Manchester

Department of Advanced Bioscience, Faculty of Agriculture, Kindai University

Masayuki Fujii, PhD, Department of Biological & Environmental Chemistry, School of Humanity Oriented Science and Technology, Kindai University

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2022

10.1089/nat.2021.0068

Nucleic Acid Therapeutics

Nucleic Acid Therapeutics

SCI
ISSN：2159-3337
年,卷(期)：2022.32(5)
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