title: Long double-stranded RNA-mediated RNA interference and immunostimulation: long interfering double-stranded RNA as a potent anticancer therapeutics.
abstract: In most applications, small interfering RNAs are designed to execute specific gene silencing via RNA interference (RNAi) without triggering nonspecific responses such as immunostimulation. However, in anticancer therapeutics, immunostimulation combined with specific oncogene silencing could be beneficial, resulting in the synergistic inhibition of cancer cell growth. In this study, we report an immunostimulatory long double-stranded RNA (dsRNA) structure with the ability to trigger RNAi-mediated specific target gene silencing, termed as long interfering dsRNA (liRNA). liRNA targeting Survivin mRNA not only efficiently and specifically triggered target gene silencing via RNAi, but also stimulated the protein kinase R pathway to induce the expression of interferon β. As a result, the ability of Survivin-targeting liRNA to inhibit cancer cell growth was superior over conventional small interfering RNA or nontargeting dsRNA structures. Our results thus provide a simple yet efficient dual function immunostimulatory RNAi-triggering structure, which is potentially applicable for the development of anticancer therapeutics.
authors.affiliation: Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University, Suwon, Korea.
authors.forename: Chan Il
authors.initials: CI
authors.lastname: Chang
authors.forename: Tae Yeon
authors.initials: TY
authors.lastname: Lee
authors.forename: Pooja
authors.initials: P
authors.lastname: Dua
authors.forename: Soyoun
authors.initials: S
authors.lastname: Kim
authors.forename: Chiang J
authors.initials: CJ
authors.lastname: Li
authors.forename: Dong-ki
authors.initials: DK
authors.lastname: Lee
mesh_terms: D015075:2-Aminopurine / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D001483:Base Sequence; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D016899:Interferon-beta / Q000276:immunology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009369:Neoplasms / Q000628:therapy*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D000077022:Survivin; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012330:RNA, Double-Stranded; D000077022:Survivin; D015075:2-Aminopurine; D016899:Interferon-beta; D019892:eIF-2 Kinase