Top

Research Article

Split Viewer

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
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

Supplementary File

Share this article on

  • line
  • mail

Related articles in Mol. Cells

Molecules and Cells

eISSN 0219-1032
qr-code Download