Oxygen tension and a pharmacological switch in the regulation of transgene expression for gene therapy

Payen, Emmanuel; Bettan, Mickaël; Henri, A; Tomkiewitcz, E.; Houque, Armelle; Kuzniak, Isabelle; Zuber, Julien; Scherman, Daniel; Beuzard, Yves

doi:10.1002/jgm.217

Cited by 32 publications

(23 citation statements)

References 43 publications

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“…Some elegant methods have been developed to directly measure HIF-1 activity by the introduction of transgenes with hypoxic response elements as promoter sequences coupled to reporter genes such as luciferase (207,208) or green fluorescent protein, GFP (209). A luciferase reporter gene under regulation of an HIF1-dependent promoter has been developed (210) for in vivo bioluminescent imaging.…”

Section: Optical Imaging Methods For Measuring Hypoxiamentioning

confidence: 99%

Molecular Imaging of Hypoxia

2008

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Section: Optical Imaging Methods For Measuring Hypoxiamentioning

confidence: 99%

Molecular Imaging of Hypoxia

2008

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“…Electrotransfer has also proved to be a valuable tool for the study of gene regulation, such as the tetracycline system, which requires at least co-transfection of two plasmids in the same cell [6]. For instance, new regulation systems of potential interest are novel doxycycline transactivators in a gene switch system [93] and a system based on hypoxiaresponsive element and tetracycline transactivators [94]. Finally, electrotransfer is a promising tool to screen for optimized secreted protein design, as has been shown in the case of TNF-α receptor variants (C. Bloquel et al, Hum Gene Ther, in press).…”

Section: Electrotransfer As a Toolmentioning

confidence: 99%

Plasmid DNA electrotransfer for intracellular and secreted proteins expression: new methodological developments and applications

et al. 2004

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SummaryIn vivo electrotransfer is a physical method of gene delivery in various tissues and organs, relying on the injection of a plasmid DNA followed by electric pulse delivery. The importance of the association between cell permeabilization and DNA electrophoresis for electrotransfer efficiency has been highlighted. In vivo electrotransfer is of special interest since it is the most efficient non-viral strategy of gene delivery and also because of its low cost, easiness of realization and safety. The potentiality of this technique can be further improved by optimizing plasmid biodistribution in the targeted organ, plasmid structure, and the design of the encoded protein. In particular, we found that plasmids of smaller size were electrotransferred more efficiently than large plasmids. It is also of importance to study and understand kinetic expression of the transgene, which can be very variable, depending on many factors including cellular localization of the protein, physiological activity and regulation. The most widely targeted tissue is skeletal muscle, because this strategy is not only promising for the treatment of muscle disorders, but also for the systemic secretion of therapeutic proteins. Vaccination and oncology gene therapy are also major fields of application of electrotransfer, whereas application to other organs such as liver, brain and cornea are expanding. Many published studies have shown that plasmid electrotransfer can lead to long-lasting therapeutic effects in various pathologies such as cancer, blood disorders, rheumatoid arthritis or muscle ischemia. DNA electrotransfer is also a powerful laboratory tool to study gene function in a given tissue.

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“…In addition, DT-A/ODD exhibited a comparable inhibitory activity of protein synthesis with DT-A in vitro, indicating that fusion of the ODD domain to DT-A does not affect its translation inhibitory activity. The ODD domain of HIF-1a has been implicated to be useful as a hypoxia switch, limiting the production of a fusion protein in normoxia while stabilizing it in hypoxia (43). For example, ODDcaspase-3 fusion protein is shown to be specifically stabilized and activated in hypoxic cells (44).…”

Section: Discussionmentioning

confidence: 99%