Highly suppressible expression of single‐chain interleukin‐12 by doxycycline following adenoviral infection with a single‐vector Tet‐regulatory system

Block, Andreas; Puls, Florian; Müller, Jürgen; Milasinovic, Dragan; Igelmann, Dana; Schäfer, Peter; Kupfermann, Nikolai; Schmoldt, A.; Ameis, Detlev; Greten, H.

doi:10.1002/jgm.334

Cited by 9 publications

(8 citation statements)

References 45 publications

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“…As demonstrated by RT-PCRs and Western blots (not shown), no transgene was expressed from this vector. The adenoviral control vector Ad.3r-Luc comprising an ubiquitously active, doxycyclin-repressible artificial promoter controlling a firefly-luciferase (Fluc) transcription unit [16] was gratefully provided by Andreas Block (Department of Medicine, UKE, Hamburg, Germany). Adenoviruses were propagated in 145-mm plates in 293 cells until 80% cytopathic response of the cells.…”

Section: Recombinant Adenovirus Acquisition and Preparationmentioning

confidence: 99%

Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour‐suppressor transgenes

Hellwinkel

Müller

Pollmann

et al. 2004

The Journal of Gene Medicine

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Section: Recombinant Adenovirus Acquisition and Preparationmentioning

confidence: 99%

Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour‐suppressor transgenes

Hellwinkel

Müller

Pollmann

et al. 2004

The Journal of Gene Medicine

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“…Thus, doxycycline could further induce rtTA and finally CD95L expression only in tyrosinase-positive melanoma cells. The function of bidirectionally, doxycycline-inducible promoters has been shown previously (47), and the transactivation of doxycycline-inducible promoters by E1A has been reported by us (9).…”

Section: Discussionmentioning

confidence: 63%

Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication‐competent CD95L adenovirus

Fecker

Schmude

Jost

et al. 2010

Experimental Dermatology

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The high mortality of melanoma demands the development of new strategies, and gene therapy may be considered provided improvements in efficacy and selectivity. Overexpression of the death ligand CD95L ⁄ FasL has been shown in previous studies as highly effective for apoptosis induction in melanoma cells. For efficient and selective targeting of melanoma, a conditional replication-competent adenoviral vector was constructed (Ad5-FFE-02), which drives CD95L expression by a tetracycline-inducible promoter. For restricting its replication to melanoma cells, the adenoviral E1A gene is controlled by a tyrosinase-derived promoter. Furthermore, adenoviral E1B was deleted and a mutated E1A was used to preferentially support replication in tumor cells. Proving its high selectivity and efficiency, strong expression of E1A and doxycycline-dependent induction of CD95L were characteristic for tyrosinase-positive melanoma cells after Ad5-FFE-02 transduction, whereas absent in non-melanoma cell lines. Importantly, Ad5-FFE-02-mediated cell lysis was restricted to melanoma cells, and induction of apoptosis was found only in tyrosinase and CD95 expressing cells. Finally, the combination of adenoviral replication and CD95L-mediated apoptosis resulted in an enhanced repression of melanoma cell growth. This new adenoviral vector may provide a basis for an efficient targeting of melanoma.

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“…An IRES-independent strategy for coordinated gene expression relies on bi-directional promoters, where a central operator-bound transactivator induces transcription from two divergently oriented minimal promoters [119,120], as exemplified by coordinated and stoichiometric expression of two transgenes in mammalian cells and mice [119][120][121][122].…”

Section: Synchronized Inducible Expression Of Several Genesmentioning

confidence: 99%

Pharmacologic transgene control systems for gene therapy

Weber

Fussenegger

2006

The Journal of Gene Medicine

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Pharmacologic transgene-expression dosing is considered essential for future gene therapy scenarios. Genetic interventions require precise transcription or translation fine-tuning of therapeutic transgenes to enable their titration into the therapeutic window, to adapt them to daily changing dosing regimes of the patient, to integrate them seamlessly into the patient's transcriptome orchestra, and to terminate their expression after successful therapy. In recent years, decisive progress has been achieved in designing high-precision trigger-inducible mammalian transgene control modalities responsive to clinically licensed and inert heterologous molecules or to endogenous physiologic signals. Availability of a portfolio of compatible transcription control systems has enabled assembly of higher-order control circuitries providing simultaneous or independent control of several transgenes and the design of (semi-)synthetic gene networks, which emulate digital expression switches, regulatory transcription cascades, epigenetic expression imprinting, and cellular transcription memories. This review provides an overview of cutting-edge developments in transgene control systems, of the design of synthetic gene networks, and of the delivery of such systems for the prototype treatment of prominent human disease phenotypes.

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Highly suppressible expression of single‐chain interleukin‐12 by doxycycline following adenoviral infection with a single‐vector Tet‐regulatory system

Abstract: With expression levels exceeding those of the cytomegalovirus (CMV) promoter in almost all cell lines tested, these new vectors will also contribute to the safety of adenoviral approaches by controlled expression without compromising on maximum expression levels.

Cited by 9 publications

References 45 publications

Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour‐suppressor transgenes

Osteosarcoma cell lines display variable individual reactions on wildtype p53 and Rb tumour‐suppressor transgenes

Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication‐competent CD95L adenovirus

Pharmacologic transgene control systems for gene therapy

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