title: Asymmetric RNA duplexes mediate RNA interference in mammalian cells.
abstract: RNA interference (RNAi) has become an indispensable technology for biomedical research and has demonstrated the potential to become a new class of therapeutic. Current RNAi technology in mammalian cells relies on short interfering RNA (siRNA) consisting of symmetrical duplexes of 19-21 base pairs (bp) with 3' overhangs. Here we report that asymmetric RNA duplexes with 3' and 5' antisense overhangs silence mammalian genes effectively. An asymmetric interfering RNA (aiRNA) of 15 bp was incorporated into the RNA-induced silencing complex (RISC) and mediated sequence-specific cleavage of the target mRNA between base 10 and 11 relative to the 5' end of the antisense strand. The gene silencing mediated by aiRNA was efficacious, durable and correlated with reduced off-target silencing by the sense strand. These results establish aiRNA as a scaffold structure for designing RNA duplexes to induce RNAi in mammalian cells.
authors.affiliation: Department of Therapeutic Biology, Boston Biomedical, Inc., 333 Providence Highway, Norwood, Massachusetts 02062, USA.
authors.forename: Xiangao
authors.initials: X
authors.lastname: Sun
authors.forename: Harry A
authors.initials: HA
authors.lastname: Rogoff
authors.forename: Chiang J
authors.initials: CJ
authors.lastname: Li
mesh_terms: D020029:Base Pairing; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference / Q000187:drug effects* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D034743:RNA-Induced Silencing Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex