title: Long-term expression of miRNA for RNA interference using a novel vector system based on a negative-strand RNA virus.
abstract: RNA interference (RNAi) has emerged as a promising technique for gene therapy. However, the safe and long-term expression of small RNA molecules is a major concern for the application of RNAi therapies in vivo. Borna disease virus (BDV), a non-segmented, negative-strand RNA virus, establishes a persistent infection without obvious cytopathic effects. Unique among animal non-retroviral RNA viruses, BDV persistently establishes a long-lasting persistent infection in the nucleus. These features make BDV ideal for RNA virus vector persistently expressing small RNAs. Here, we demonstrated that the recombinant BDV (rBDV) containing the miR-155 precursor, rBDV-miR-155, persistently expressed miR-155 and efficiently silenced its target gene. The stem region of the miR-155 precursor in rBDV-miR-155 was replaceable by any miRNA sequences of interest and that such rBDVs efficiently silence the expression of target genes. Collectively, BDV vector would be a novel RNA virus vector enabling the long-term expression of miRNAs for RNAi therapies.
authors.affiliation: Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.|Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Honda
authors.affiliation: Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.|Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Daito
authors.affiliation: Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.|Center for Emerging Virus Research, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Makino
authors.affiliation: Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.|Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, Kyoto 606-8507, Japan.|Department of Tumor Viruses, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto 606-8507, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Tomonaga
mesh_terms: D000818:Animals; D001891:Borna disease virus / Q000235:genetics*; D002522:Chlorocebus aethiops; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008967:Molecular Biology / Q000379:methods*; D034622:RNA Interference; D014709:Vero Cells
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs