Robust and efficient regulation of transgene expression in vivo by improved tetracycline-dependent lentiviral vectors

Elisa Vigna, Simona Cavalieri, Laurie Ailles, Massimo Geuna, Rainer Loew, Hermann Bujard, Luigi Naldini

Research output: Contribution to journalArticlepeer-review

Abstract

We developed a panel of lentiviral vectors that displayed tetracycline-regulated transgene expression over two orders of magnitude in bulk, non-selected populations of transduced cells in vitro and in vivo. The robust expression and homogeneous response indicated that most transduced vector genomes were transcription competent and responsive to regulation, providing the lentiviral vector with a novel competitive advantage for gene transfer. After ex vivo transduction and transplantation of cord blood CD34+ cells into NOD/SCID mice, reporter gene expression could be switched "on" and "off" in human hematopoietic cells in vivo for prolonged times, proving integration of the regulated expression system into long-term repopulating cells. By vector injection into established tumor grafts, we achieved efficient delivery and quantitative regulation of transgene expression in vivo. By these approaches, gene function studies can now be performed in in vivo models of human hematopoiesis and cancer. In the future, regulated lentiviral vectors will improve the safety and efficacy of gene therapy.

Original languageEnglish
Pages (from-to)252-261
Number of pages10
JournalMolecular Therapy
Volume5
Issue number3
DOIs
Publication statusPublished - 2002

Keywords

  • Gene therapy
  • Hematopoietic stem cells
  • Lentiviral vectors
  • Tet-regulated system

ASJC Scopus subject areas

  • Molecular Biology

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