title: In Vivo RNAi Efficacy of Palmitic Acid-Conjugated Dicer-Substrate siRNA in a Subcutaneous Tumor Mouse Model.
abstract: Short interfering RNAs are used in RNA interference technology and are powerful tools for target gene silencing in a sequence-specific manner. In this study, we synthesized Dicer-substrate siRNAs consisting of 27-nt double-stranded RNAs conjugated with palmitic acid at the 5'-end of the sense strand and investigated their RNA interference efficacies in vitro and in vivo. The palmitic acid-conjugated 27-nt DsiRNAs (C16-Dsi27RNAs) were prepared by our simple synthesis strategy and achieved a good yield. C16-Dsi27RNAs showed enhanced in vitro RNA interference potency compared with not only non-modified Dsi27RNAs but also cholesterol-conjugated Dsi27RNAs against both an exogenous enhanced green fluorescent protein and the endogenous vascular endothelial growth factor gene in a human scirrhous-type gastric cancer cell line that stably expressed the enhanced green fluorescent protein gene (GCIY-eGFP). Additionally, C16-Dsi27RNAs had potent gene silencing activity against both enhanced green fluorescent protein and vascular endothelial growth factor as target genes in a subcutaneous tumor mouse model generated from GCIY-eGFP cells administered by intratumoral injection. These results suggest that the C16-Dsi27RNAs will be useful next-generation RNA interference molecules that can overcome the problems associated with RNA interference technology.
authors.affiliation: Laboratory of Molecular Cell Biology, Department of Life Sciences, Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima, 731-0153, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Laboratory of Molecular Cell Biology, Department of Life Sciences, Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima, 731-0153, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Seyama
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D019308:Palmitic Acid / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D019308:Palmitic Acid; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Dicer-substrate siRNA; enhanced green fluorescent protein; in vivo RNAi activity; lipid-conjugated siRNAs; potent gene silencing; vascular endothelial growth factor