RNA Virus-Based Episomal Vector with a Fail-Safe Switch Facilitating Efficient Genetic Modification and Differentiation of iPSCs

Yumiko Komatsu, Dan Takeuchi, Tomoya Tokunaga, Hidetoshi Sakurai, Akiko Makino, Tomoyuki Honda, Yasuhiro Ikeda, Keizo Tomonaga

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

A gene delivery system that allows efficient and safe stem cell modification is critical for next-generation stem cell therapies. An RNA virus-based episomal vector (REVec) is a gene transfer system developed based on Borna disease virus (BoDV), which facilitates persistent intranuclear RNA transgene delivery without integrating into the host genome. In this study, we analyzed susceptibility of human induced pluripotent stem cell (iPSC) lines from different somatic cell sources to REVec, along with commonly used viral vectors, and demonstrated highly efficient REVec transduction of iPSCs. Using REVec encoding myogenic transcription factor MyoD1, we further demonstrated potential application of the REVec system for inducing differentiation of iPSCs into skeletal muscle cells. Of note, treatment with a small molecule, T-705, completely eliminated REVec in persistently transduced cells. Thus, the REVec system offers a versatile toolbox for stable, integration-free iPSC modification and trans-differentiation, with a unique switch-off mechanism.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalMolecular Therapy - Methods and Clinical Development
Volume14
DOIs
StatePublished - Sep 13 2019

Keywords

  • RNA virus
  • episomal vector
  • iPSCs

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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