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Mol. Cells 2009; 27(6): 689-695

Published online June 30, 2009

https://doi.org/10.1007/s10059-009-0093-0

© The Korean Society for Molecular and Cellular Biology

Dual-Target Gene Silencing by Using Long,Synthetic siRNA Duplexes without Triggering Antiviral Responses

Chan Il Chang, Hye Suk Kang, Changill Ban, Soyoun Kim, and Dong-ki Lee

Received: May 6, 2009; Revised: May 20, 2009; Accepted: May 20, 2009

Abstract

Chemically synthesized small interfering RNAs (siRNAs) can specifically knock-down expression of target genes via RNA interference (RNAi) pathway. To date, the length of synthetic siRNA duplex has been strictly maintained less than 30 bp, because an early study suggested that double-stranded RNAs (dsRNAs) longer than 30 bp could not trigger specific gene silencing due to the induction of non-specific antiviral interferon responses. Contrary to the current belief, here we show that synthetic dsRNA as long as 38 bp can result in specific target gene silencing without non-specific antiviral responses. Using this longer duplex structure, we have generated dsRNAs, which can simultaneously knock-down expression of two target genes (termed as dual-target siRNAs or dsiRNAs). Our results thus demonstrate the structural flexibility of gene silencing siRNAs, and provide a starting point to construct multifunctional RNA structures. The dsiRNAs could be utilized to develop a novel therapeutic gene silencing strategy against diseases with multiple gene alternations such as viral infection and cancer.

Keywords antiviral response, dual target, off-target effect, RNA interference, siRNA

Article

Research Article

Mol. Cells 2009; 27(6): 689-695

Published online June 30, 2009 https://doi.org/10.1007/s10059-009-0093-0

Copyright © The Korean Society for Molecular and Cellular Biology.

Dual-Target Gene Silencing by Using Long,Synthetic siRNA Duplexes without Triggering Antiviral Responses

Chan Il Chang, Hye Suk Kang, Changill Ban, Soyoun Kim, and Dong-ki Lee

Received: May 6, 2009; Revised: May 20, 2009; Accepted: May 20, 2009

Abstract

Chemically synthesized small interfering RNAs (siRNAs) can specifically knock-down expression of target genes via RNA interference (RNAi) pathway. To date, the length of synthetic siRNA duplex has been strictly maintained less than 30 bp, because an early study suggested that double-stranded RNAs (dsRNAs) longer than 30 bp could not trigger specific gene silencing due to the induction of non-specific antiviral interferon responses. Contrary to the current belief, here we show that synthetic dsRNA as long as 38 bp can result in specific target gene silencing without non-specific antiviral responses. Using this longer duplex structure, we have generated dsRNAs, which can simultaneously knock-down expression of two target genes (termed as dual-target siRNAs or dsiRNAs). Our results thus demonstrate the structural flexibility of gene silencing siRNAs, and provide a starting point to construct multifunctional RNA structures. The dsiRNAs could be utilized to develop a novel therapeutic gene silencing strategy against diseases with multiple gene alternations such as viral infection and cancer.

Keywords: antiviral response, dual target, off-target effect, RNA interference, siRNA

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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