title: MicroRNA-regulated transgene expression systems for gene therapy and virotherapy.
abstract: For safe and effective gene therapy, targeted tissue-restricted transgene expression is desirable. Various methods have been developed to achieve such expression, including the use of tissue-specific promoters. In addition to these approaches, a new system which can regulate transgene expression, including viral gene expression, by exploiting microRNAs (miRNAs) has recently been developed. miRNAs are approximately 22-nucleotide (nt)-long non-coding RNAs that translationally suppress or catalytically degrade target mRNA through binding to imperfectly complementary sequences in the 3'-untranslated region (UTR). In miRNA-regulated transgene expression systems, tandem copies of sequences perfectly complementary to the miRNAs are usually incorporated into the 3'-UTR of the transgene expression cassette, leading to the suppression of transgene expression in cells expressing the corresponding miRNAs. miRNA-mediated regulation of transgene expression was first demonstrated for lentivirus vectors, and subsequently this technology was applied to replication-incompetent adenovirus vectors, tumor-specific oncolytic viruses for cancer therapy, and recombinant live attenuated viruses for vaccine therapy. The aim of this review is to highlight the applications of miRNA-regulated transgene expression systems for gene therapy and virotherapy.
authors.affiliation: Department of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan. sakurai@phs.osaka-u.ac.jp
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sakurai
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Katayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
mesh_terms: D020413:3' Untranslated Regions; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015870:Gene Expression; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D050130:Oncolytic Virotherapy / Q000379:methods*; D034622:RNA Interference; D014779:Virus Replication
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs