In vivo transduction of HIV-1-derived lentiviral particles engineered for macrolide-adjustable transgene expression.
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.
Mitta
Barbara
B
Institute for Chemical and Bio-Engineering, Swiss Federal Institute of Technology, ETH Hoenggerberg, HCI F115, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Weber
Cornelia C
CC
Fussenegger
Martin
M
D000818:Animals; D016466:CHO Cells; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000502:physiology; D006224:Cricetinae; D005786:Gene Expression Regulation; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism*; D018942:Macrolides / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D018942:Macrolides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A