PMID- 15999397 OWN - NLM STAT- MEDLINE DCOM- 20060203 LR - 20141120 IS - 1099-498X (Print) IS - 1099-498X (Linking) VI - 7 IP - 11 DP - 2005 Nov TI - In vivo transduction of HIV-1-derived lentiviral particles engineered for macrolide-adjustable transgene expression. PG - 1400-8 AB - 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. CI - Copyright (c) 2005 John Wiley & Sons, Ltd. FAU - Mitta, Barbara AU - Mitta B AD - Institute for Chemical and Bio-Engineering, Swiss Federal Institute of Technology, ETH Hoenggerberg, HCI F115, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland. FAU - Weber, Cornelia C AU - Weber CC FAU - Fussenegger, Martin AU - Fussenegger M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Gene Med JT - The journal of gene medicine JID - 9815764 RN - 0 (Macrolides) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Animals MH - CHO Cells MH - Chick Embryo MH - Chorioallantoic Membrane/blood supply/physiology MH - Cricetinae MH - *Gene Expression Regulation MH - *Genetic Engineering MH - Genetic Vectors/genetics/metabolism MH - HIV-1/*genetics MH - Humans MH - In Vitro Techniques MH - Lentivirus/genetics/*metabolism MH - Macrolides/metabolism MH - *Transduction, Genetic MH - *Transgenes MH - Vascular Endothelial Growth Factor A/genetics/metabolism EDAT- 2005/07/07 09:00 MHDA- 2006/02/04 09:00 CRDT- 2005/07/07 09:00 PHST- 2005/07/07 09:00 [pubmed] PHST- 2006/02/04 09:00 [medline] PHST- 2005/07/07 09:00 [entrez] AID - 10.1002/jgm.798 [doi] PST - ppublish SO - J Gene Med. 2005 Nov;7(11):1400-8. doi: 10.1002/jgm.798.