title: Switching on the lights for gene therapy.
abstract: 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.
authors.affiliation: Laboratory for Gene Therapy and Molecular Imaging at the Max Planck-Institute for Neurological Research, Center for Molecular Medicine (CMMC) and Department of Neurology, University of Cologne, Cologne, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Winkeler
authors.forename: Miguel
authors.initials: M
authors.lastname: Sena-Esteves
authors.forename: Leonie E M
authors.initials: LE
authors.lastname: Paulis
authors.forename: Hongfeng
authors.initials: H
authors.lastname: Li
authors.forename: Yannic
authors.initials: Y
authors.lastname: Waerzeggers
authors.forename: Benedikt
authors.initials: B
authors.lastname: Rückriem
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.forename: Markus
authors.initials: M
authors.lastname: Klein
authors.forename: Parisa
authors.initials: P
authors.lastname: Monfared
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rueger
authors.forename: Michael
authors.initials: M
authors.lastname: Heneka
authors.forename: Stefan
authors.initials: S
authors.lastname: Vollmar
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.forename: Cornel
authors.initials: C
authors.lastname: Fraefel
authors.forename: Rudolf
authors.initials: R
authors.lastname: Graf
authors.forename: Klaus
authors.initials: K
authors.lastname: Wienhard
authors.forename: Wolf D
authors.initials: WD
authors.lastname: Heiss
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D049449:Luminescence; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase