Long-term expression of miRNA for RNA interference using a novel vector system based on a negative-strand RNA virus

Tomoyuki Honda, Yusuke Yamamoto, Takuji Daito, Yusuke Matsumoto, Akiko Makino, Keizo Tomonaga

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Article number26154
JournalScientific reports
Volume6
DOIs
Publication statusPublished - May 18 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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