Open Access
MicroRNA-regulated transgene expression systems for gene therapy and virotherapy
Fuminori Sakurai1,Kazufumi Katayama1,Hiroyuki Mizuguchi1
Department of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
DOI: 10.2741/3861 Volume 16 Issue 6, pp.2389-2401
Published: 01 June 2011

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.

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Fuminori Sakurai, Kazufumi Katayama, Hiroyuki Mizuguchi. MicroRNA-regulated transgene expression systems for gene therapy and virotherapy. Frontiers in Bioscience-Landmark. 2011. 16(6); 2389-2401.