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Novel hyperactive transposons for genetic modification of induced puripotent and adult stem cells: a non-viral paradigm for coaxed differentiation

Item Type:Article
Title:Novel hyperactive transposons for genetic modification of induced puripotent and adult stem cells: a non-viral paradigm for coaxed differentiation
Creators Name:Belay, E. and Matrai, J. and Acosta-Sanchez, A. and Ma, L. and Quattrocelli, M. and Mates, L. and Sancho-Bru, P. and Geraerts, M. and Yan, B. and Vermeesch, J. and Rincon, M.Y. and Samara-Kuko, E. and Ivics, Z. and Verfaillie, C.M. and Sampaolesi, M. and Izsvak, Z. and Vandendriessche, T. and Chuah, M.K.
Abstract:Adult stem cells and induced pluripotent stem cells (iPS) hold great promise for regenerative medicine. The development of robust non-viral approaches for stem cell gene transfer would facilitate functional studies and potential clinical applications. We have previously generated hyperactive transposases derived from Sleeping Beauty, using an in vitro molecular evolution and selection paradigm. We now demonstrate that these hyperactive transposases resulted in superior gene transfer efficiencies and expression in mesenchymal and muscle stem/progenitor cells, consistent with higher expression levels of therapeutically relevant proteins including coagulation factor IX. Their differentiation potential and karyotype was not affected. Moreover, stable transposition could also be achieved in iPS which retained their ability to differentiate along neuronal, cardiac and hepatic lineages without causing cytogenetic abnormalities. Most importantly, transposon-mediated delivery of the myogenic PAX3 transcription factor into iPS coaxed their differentiation into MYOD(+) myogenic progenitors and multinucleated myofibers, suggesting that PAX3 may serve as a myogenic "molecular switch" in iPS. Hence, this hyperactive transposon system represents an attractive non-viral gene transfer platform with broad implications for regenerative medicine, cell and gene therapy.
Keywords:Transposon, Sleeping Beauty, iPS, Myoblast, Stem Cell, Mesenchymal Stem Cell, Muscle, Animals, Mice
Source:Stem Cells
ISSN:1066-5099
Publisher:Alphamed Press (U.S.A.)
Volume:28
Number:10
Page Range:1760-1771
Date:October 2010
Official Publication:https://doi.org/10.1002/stem.501
PubMed:View item in PubMed

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