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  • Title: In vivo transduction of HIV-1-derived lentiviral particles engineered for macrolide-adjustable transgene expression.
    Author: Mitta B, Weber CC, Fussenegger M.
    Journal: J Gene Med; 2005 Nov; 7(11):1400-8. PubMed ID: 15999397.
    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.
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