title: Long DNA passenger strand highly improves the activity of RNA/DNA hybrid siRNAs.
abstract: Small interfering RNAs (siRNAs) are potent tools in biomedical research, which can reduce the expression level of target proteins through RNAi pathway. They are composed of 19-25 bp double strand RNA (dsRNAs), therefore, stimulate dsRNAs dependent interferon responses in a non-specific manner. This problem has prevented siRNAs from being applied as new therapeautic agents. In the present paper, we tried to circumvent interferon responses using RNA/DNA hetero siRNAs (HsiRNAs) composed of RNA guide and DNA passenger strands. It was previously reported that siRNAs which were partially substituted with DNA had RNAi activity and that DNA substitution often caused the activity loss. In our results, HsiRNAs, in which the passenger strand of siRNAs were exchanged with DNA also showed much lower activity than that of parental siRNAs. Here, we found that attachment of 5' flanking sequence to DNA passenger strand improved the activity of HsiRNAs. Furthermore, the effective HsiRNAs induced much lower interferon responses than parental siRNAs. Thus, HsiRNAs with 5' flanking sequence are expected to be novel siRNA drug candidates.
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku, Osaka 558-8585, Japan. Electronic address: ida@bioa.eng.osaka-cu.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tachibana
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Toshizumi
authors.initials: T
authors.lastname: Tanabe
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D006147:Guanine / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000276:immunology; D009693:Nucleic Acid Hybridization; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D006147:Guanine; D004247:DNA; D007372:Interferons
keywords: DNA; Guanine; HsiRNA; RNAi; siRNA