TY - JOUR
T1 - RNA Virus-Based Episomal Vector with a Fail-Safe Switch Facilitating Efficient Genetic Modification and Differentiation of iPSCs
AU - Komatsu, Yumiko
AU - Takeuchi, Dan
AU - Tokunaga, Tomoya
AU - Sakurai, Hidetoshi
AU - Makino, Akiko
AU - Honda, Tomoyuki
AU - Ikeda, Yasuhiro
AU - Tomonaga, Keizo
N1 - Funding Information:
We thank Jason M.T. and Claire A.S. at the Mayo Clinic for technical support and for preparing AAV2, Ad5, and lentiviral vectors. We thank Dr. Maria L. and Chantel R. at the Memorial University of Newfoundland for proofreading of the manuscript. This work was supported in part by a start-up grant (Y.K.) from The Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research (K-CONNEX); JSPS KAKENHI grant numbers JP18K18385 (to Y.K.) and JP17H04083 (to K.T.); MEXT KAKENHI grant numbers JP16H06429 , JP16K21723 , and JP16H06430 (to K.T.); MEXT Core-to-Core Program A ; the Advanced Research Networks (to K.T.); and AMED grant numbers JP18am0301015 (to K.T.) and JP18fm020814 (to K.T.).
Publisher Copyright:
© 2019 The Author(s)
PY - 2019/9/13
Y1 - 2019/9/13
N2 - 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.
AB - 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.
KW - RNA virus
KW - episomal vector
KW - iPSCs
UR - http://www.scopus.com/inward/record.url?scp=85067846526&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067846526&partnerID=8YFLogxK
U2 - 10.1016/j.omtm.2019.05.010
DO - 10.1016/j.omtm.2019.05.010
M3 - Article
AN - SCOPUS:85067846526
SN - 2329-0501
VL - 14
SP - 47
EP - 55
JO - Molecular Therapy - Methods and Clinical Development
JF - Molecular Therapy - Methods and Clinical Development
ER -
