Article

In vivo transduction of HIV-1-derived lentiviral particles engineered for macrolide-adjustable transgene expression.

Institute for Chemical and Bio-Engineering, Swiss Federal Institute of Technology, ETH Hoenggerberg, HCI F115, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
The Journal of Gene Medicine (impact factor: 2.48). 12/2005; 7(11):1400-8. DOI:10.1002/jgm.798 pp.1400-8
Source: PubMed

ABSTRACT The molecular merger of latest-generation transduction technologies with advanced transgene control modalities may foster decisive advances in therapeutic reprogramming of somatic cell phenotypes.
We have engineered self-inactivating HIV-1-based lentiviral expression vectors for reversible macrolide-adjustable transgene expression.
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.
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.

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Keywords

different human primary cells
 
future gene therapy trials
 
isogenic streptogramin-
 
Macrolide-adjustable lentivectors
 
macrolide-controlled VEGF121 production exhibited dose-dependent neovascularization
 
macrolide-responsive human vascular endothelial growth factor 121
 
mammalian cell lines
 
molecular merger
 
precise
 
reversible macrolide-adjustable transgene expression
 
self-inactivating HIV-1-based lentiviral expression vectors
 
therapeutic reprogramming
 
transgene control modalities
 
vivo
 
vivo transgene fine-tuning
 

Barbara Mitta