Year : 2007 Switching on the lights for gene therapy

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application. Switching on the Lights for Gene Therapy Alexandra Winkeler, Miguel Sena-Esteves, Leonie E. M. Paulis, Hongfeng Li, Yannic Waerzeggers, Benedikt Rückriem, Uwe Himmelreich, Markus Klein, Parisa Monfared, Maria A. Rueger, Michael Heneka, Stefan Vollmar, Mathias Hoehn, Cornel Fraefel, Rudolf Graf, Klaus Wienhard, Wolf D. Heiss, Andreas H. Jacobs* Laboratory for Gene Therapy and Molecular Imaging at the Max Planck-Institute for Neurological Research, Center for Molecular Medicine (CMMC) and Departments of Neurology and Radiology at the University of Cologne, Cologne, Germany Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to noninvasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application. Citation: Winkeler A, Sena-Esteves M, Paulis LEM, Li H, Waerzeggers Y, et al (2007) Switching on the Lights for Gene Therapy. PLoS ONE 2(6): e528. doi:10.1371/journal.pone. 0000528