title: The sense strand pre-cleaved RNA duplex mediates an efficient RNA interference with less off-target and immune response effects.
abstract: RNA interference is an appealing and promising therapeutic approach in cancer and other diseases. Designing novel strategies aiming to increase the efficiency, duration, and reduce the off-target silencing by sense strand is of great significance for its future application clinically. Here, we report that RNA duplex with the sense strand pre-cleaved at the base between base 10 and 11 relative to the 5' end of the antisense strand induced a target-specific RNA silencing effectively. Furthermore, different from the canonical RNA duplex, this novel RNA duplex rarely inhibits the luciferase activity in the reporter, bearing the target sequence corresponding to the sense strand, suggesting a less off-target effects of this novel strategy. Furthermore, the immune response of the novel RNA duplex induced a much milder immune response as seen from the NFkappaB activity. In addition, our newly designed RNA duplex should be easier for preservation than the asymmetric RNA duplex. Our results establish a novel method to design a new class of RNA duplex for improved RNA interference.
authors.affiliation: Department of Biochemistry and Molecular Biology, The State Key Laboratory of Cancer Biology, The Fourth Military Medical University, No. 17 Changlexi Road, 710032, Xi'an, People's Republic of China.
authors.forename: Xiaozhao
authors.initials: X
authors.lastname: Lu
authors.forename: Guodong
authors.initials: G
authors.lastname: Yang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Fu
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.forename: Mengying
authors.initials: M
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zifan
authors.initials: Z
authors.lastname: Lu
mesh_terms: D002478:Cells, Cultured; D055785:Gene Knockdown Techniques / Q000379:methods*; D019073:HT29 Cells; D006801:Humans; D007109:Immunity; D016328:NF-kappa B / Q000032:analysis / Q000378:metabolism; D012313:RNA / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D034741:RNA, Small Interfering; D012313:RNA