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Mol. Cells 2011; 32(6): 543-548

Published online November 3, 2011

https://doi.org/10.1007/s10059-011-0160-1

© The Korean Society for Molecular and Cellular Biology

Selection and Optimization of Asymmetric siRNA Targeting the Human c-MET Gene

Seul-gi Jo1,3, Sun Woo Hong1,2,3, Jae Wook Yoo1, Chang Han Lee1, Sera Kim1, Soyoun Kim2, and Dong-ki Lee1,*

1Global Research Laboratory for RNAi Medicine, Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University, Suwon 440-746, Korea, 2Department of Biomedical Engineering, Dongguk University, Seoul 100-715, Korea, 3These authors contributed equally to this work.

Correspondence to : *Correspondence: dklee@skku.edu

Received: August 1, 2011; Revised: September 15, 2011; Accepted: September 19, 2011

Abstract

The silencing of specific oncogenes via RNA interference (RNAi) holds great promise for the future of cancer therapy. RNAi is commonly carried out using small interfering RNA (siRNA) composed of a 19 bp duplex region with a 2-nucleotide overhang at each 3’ end. This classical siRNA structure, however, can trigger non-specific effects, which has hampered the development of specific and safe RNAi therapeutics. Previously, we developed a novel siRNA structure, called asymmetric shorter-duplex siRNA (asiRNA), which did not cause the non-specific effects triggered by conventional siRNA, such as off-target gene silencing mediated by the sense strand. In this study, we first screened potent asiRNA molecules targeting the human c-MET gene, a promising anticancer target. Next, the activity of a selected asiRNA was further optimized by introducing a locked nucleic acid (LNA) to maximize the gene silencing potency. The optimized asiRNA targeted to c-MET may have potential as a specific and safe anticancer RNAi therapeutic.

Keywords asiRNA, cancer, c-MET, RNA interference, siRNA

Article

Research Article

Mol. Cells 2011; 32(6): 543-548

Published online December 31, 2011 https://doi.org/10.1007/s10059-011-0160-1

Copyright © The Korean Society for Molecular and Cellular Biology.

Selection and Optimization of Asymmetric siRNA Targeting the Human c-MET Gene

Seul-gi Jo1,3, Sun Woo Hong1,2,3, Jae Wook Yoo1, Chang Han Lee1, Sera Kim1, Soyoun Kim2, and Dong-ki Lee1,*

1Global Research Laboratory for RNAi Medicine, Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University, Suwon 440-746, Korea, 2Department of Biomedical Engineering, Dongguk University, Seoul 100-715, Korea, 3These authors contributed equally to this work.

Correspondence to:*Correspondence: dklee@skku.edu

Received: August 1, 2011; Revised: September 15, 2011; Accepted: September 19, 2011

Abstract

The silencing of specific oncogenes via RNA interference (RNAi) holds great promise for the future of cancer therapy. RNAi is commonly carried out using small interfering RNA (siRNA) composed of a 19 bp duplex region with a 2-nucleotide overhang at each 3’ end. This classical siRNA structure, however, can trigger non-specific effects, which has hampered the development of specific and safe RNAi therapeutics. Previously, we developed a novel siRNA structure, called asymmetric shorter-duplex siRNA (asiRNA), which did not cause the non-specific effects triggered by conventional siRNA, such as off-target gene silencing mediated by the sense strand. In this study, we first screened potent asiRNA molecules targeting the human c-MET gene, a promising anticancer target. Next, the activity of a selected asiRNA was further optimized by introducing a locked nucleic acid (LNA) to maximize the gene silencing potency. The optimized asiRNA targeted to c-MET may have potential as a specific and safe anticancer RNAi therapeutic.

Keywords: asiRNA, cancer, c-MET, RNA interference, siRNA

Mol. Cells
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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