Barbara Mitta1, Cornelia C Weber, Martin Fussenegger. 1. Institute for Chemical and Bio-Engineering, Swiss Federal Institute of Technology, ETH Hoenggerberg, HCI F115, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Abstract
BACKGROUND: The molecular merger of latest-generation transduction technologies with advanced transgene control modalities may foster decisive advances in therapeutic reprogramming of somatic cell phenotypes. METHODS: We have engineered self-inactivating HIV-1-based lentiviral expression vectors for reversible macrolide-adjustable transgene expression. RESULTS: Lentiviral particles engineered for macrolide-responsive human vascular endothelial growth factor 121 (VEGF121) expression compared favourably with isogenic streptogramin- and tetracycline-responsive configurations and showed excellent growth-factor fine-tuning following transduction into a variety of mammalian cell lines and different human primary cells. Chicken embryos transduced for macrolide-controlled VEGF121 production exhibited dose-dependent neovascularization and exemplified lentivector-delivered transgene transcription fine-tuning in vivo. CONCLUSIONS: Macrolide-adjustable lentivectors enable robust and precise in vitro and in vivo transgene fine-tuning which may give future gene therapy trials a new impetus. Copyright (c) 2005 John Wiley & Sons, Ltd.
BACKGROUND: The molecular merger of latest-generation transduction technologies with advanced transgene control modalities may foster decisive advances in therapeutic reprogramming of somatic cell phenotypes. METHODS: We have engineered self-inactivating HIV-1-based lentiviral expression vectors for reversible macrolide-adjustable transgene expression. RESULTS: Lentiviral particles engineered for macrolide-responsive human vascular endothelial growth factor 121 (VEGF121) expression compared favourably with isogenic streptogramin- and tetracycline-responsive configurations and showed excellent growth-factor fine-tuning following transduction into a variety of mammalian cell lines and different human primary cells. Chicken embryos transduced for macrolide-controlled VEGF121 production exhibited dose-dependent neovascularization and exemplified lentivector-delivered transgene transcription fine-tuning in vivo. CONCLUSIONS:Macrolide-adjustable lentivectors enable robust and precise in vitro and in vivo transgene fine-tuning which may give future gene therapy trials a new impetus. Copyright (c) 2005 John Wiley & Sons, Ltd.
Authors: Murilo T D Bueno; Daniel Reyes; Luis Valdes; Adarsh Saheba; Eduardo Urias; Crystal Mendoza; Oliver I Fregoso; Manuel Llano Journal: J Virol Date: 2012-12-19 Impact factor: 5.103