title: Overcoming the challenges of siRNA activation of innate immunity: design better therapeutic siRNAs.
abstract: RNA interference (RNAi) is a conserved regulatory mechanism of posttranscriptional gene silencing triggered by either endogenously (e.g. microRNAs) or exogenously double-stranded RNA as small interfering (si) RNAs. To date, the use of siRNA (21-nt) has become a standard laboratory tool to silence gene expression in mammalian cells in-vitro and in-vivo. The methodology also holds promise for treating a diversity of human diseases. However, one of the challenges of making siRNAs as therapeutic drugs includes the activation of innate immunity and silencing of unwanted genes. Therefore, the use of siRNAs in functional genomics and human therapies depends on the development of strategies to overcome siRNA unwanted effects. This chapter highlights some efficient strategies aimed at separating gene silencing from immunostimulation and improving siRNA gene silencing specificity.
authors.affiliation: Department of Immunology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, N-310, Norway, Mouldy.Sioud@rr-research.no.
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D015972:Gene Expression Regulation, Neoplastic; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering / Q000138:chemical synthesis / Q000235:genetics* / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000276:immunology; D012266:Ribose / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C437968:PLAAT4 protein, human; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D018168:Receptors, Retinoic Acid; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors; D012266:Ribose