Novel hyperactive transposons for genetic modification of induced pluripotent and adult stem cells: A nonviral paradigm for coaxed differentiation

Eyayu Belay, Janka Mátrai, Abel Acosta-Sanchez, Ling Ma, Mattia Quattrocelli, Lajos Mátés, Pau Sancho-Bru, Martine Geraerts, Bing Yan, Joris Vermeesch, Melvin Yesid Rincón, Ermira Samara-Kuko, Zoltán Ivics, Catherine Verfaillie, Maurilio Sampaolesi, Zsuzsanna Izsvák, Thierry Vandendriessche, Marinee K.L. Chuah

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Adult stem cells and induced pluripotent stem cells (iPS) hold great promise for regenerative medicine. The development of robust nonviral 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, transposonmediated 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 nonviral gene transfer platform with broad implications for regenerative medicine, cell and gene therapy.

Original languageEnglish
Pages (from-to)1760-1771
Number of pages12
JournalStem Cells
Volume28
Issue number10
DOIs
Publication statusPublished - Oct 1 2010

Keywords

  • Mesenchymal stem cell
  • Muscle
  • Myoblast
  • Sleeping beauty
  • Stem cell
  • Transposon
  • iPS

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Belay, E., Mátrai, J., Acosta-Sanchez, A., Ma, L., Quattrocelli, M., Mátés, L., Sancho-Bru, P., Geraerts, M., Yan, B., Vermeesch, J., Rincón, M. Y., Samara-Kuko, E., Ivics, Z., Verfaillie, C., Sampaolesi, M., Izsvák, Z., Vandendriessche, T., & Chuah, M. K. L. (2010). Novel hyperactive transposons for genetic modification of induced pluripotent and adult stem cells: A nonviral paradigm for coaxed differentiation. Stem Cells, 28(10), 1760-1771. https://doi.org/10.1002/stem.501