title: Delivery and inhibition of reporter genes by small interfering RNAs in a mouse skin model.
abstract: RNA interference offers the potential of a novel therapeutic approach for treating skin disorders. To this end, we investigated delivery of nucleic acids, including a plasmid expressing the reporter gene luciferase, to mouse skin by intradermal injection into footpads using in vivo bioluminescence imaging over multiple time points. In order to evaluate the ability of RNA interference to inhibit skin gene expression, reporter gene constructs were co-injected with specific or non-specific siRNAs and the in vivo effects measured. Our results revealed that specific unmodified and modified siRNAs (but not nonspecific matched controls) strongly inhibit reporter gene expression in mice. These results indicate that small interfering RNA, delivered locally as RNA directly or expressed from viral or non-viral vectors, may be effective agents for treating skin disorders.
authors.affiliation: Molecular Imaging Program at Stanford, and Department of Radiology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Heini
authors.initials: H
authors.lastname: Ilves
authors.forename: Pauline
authors.initials: P
authors.lastname: Chu
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Contag
authors.forename: Devin
authors.initials: D
authors.lastname: Leake
authors.forename: Brian H
authors.initials: BH
authors.lastname: Johnston
authors.forename: Roger L
authors.initials: RL
authors.lastname: Kaspar
mesh_terms: D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology; D008156:Luciferases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010957:Plasmids; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D012867:Skin / Q000166:cytology / Q000201:enzymology*; D013997:Time Factors
chemical_list: D034741:RNA, Small Interfering; D008156:Luciferases