title: Selection and optimization of asymmetric siRNA targeting the human c-MET gene.
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.
authors: Global Research Laboratory for RNAi Medicine, Department of Chemistry and Brain Korea 21 School of Chemical Materials Science, Sungkyunkwan University, Suwon 440-746, Korea.
authors: Seul-gi
authors: SG
authors: Jo
authors: Sun Woo
authors: SW
authors: Hong
authors: Jae Wook
authors: JW
authors: Yoo
authors: Chang Han
authors: CH
authors: Lee
authors: Sera
authors: S
authors: Kim
authors: Soyoun
authors: S
authors: Kim
authors: Dong-ki
authors: DK
authors: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D009841:Oligonucleotides / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009841:Oligonucleotides; D034741:RNA, Small Interfering; C477371:locked nucleic acid; D008156:Luciferases; D019859:Proto-Oncogene Proteins c-met