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.