Key result
A novel gene regulation system using human PPAR gamma and oral PPAR gamma activators induced reporter gene expression more than 25-fold in rodent skeletal muscle and myocardium.
Why the study?
A gene regulation system using human PPAR gamma and clinically approved activators for gene therapy had not been developed or demonstrated in skeletal muscle and heart.
Does a gene regulation system using human PPAR gamma and oral PPAR gamma activators induce reporter gene expression in rodent skeletal muscle and myocardium?
Does a gene regulation system using human PPAR gamma and oral PPAR gamma activators induce reporter gene expression in rodent skeletal muscle and myocardium?
Effect estimate: >25-fold induction
A novel gene regulation system using human PPAR gamma and oral thiazolidinediones enables robust, dose-dependent, and repeatable induction of gene expression in rodent myocardium and skeletal muscle.
May enable regulated gene expression in rodent muscle and heart; leaves open translation to human gene therapy.
We have developed a new gene regulation system for gene therapy. This system consists of two expression cassettes; one expresses the human peroxisome proliferator-activated receptor gamma(PPAR gamma), and the other expresses the therapeutic gene under the control of multiple peroxisome proliferator-activated receptor (PPAR) response elements (PPREs) linked to a basal promoter. Using direct injection of plasmid DNA into skeletal muscle or myocardium of rodents and oral administration of clinically approved PPAR gamma activators, we demonstrate that reporter gene expression can be induced more than 25-fold. We show that oral administration of PPAR gamma activator at intervals separated by several months results in repeated pulses of high-level reporter gene expression. We also document a PPAR gamma activator dose-response effect on reporter gene expression. This is the first report of a gene regulation system that makes use of a human transcription factor and that may be safer than chimeric transcription factors for human gene therapy.
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Darteil et al. (2002) studied Gene therapy. PPAR gamma gene regulation system and oral PPAR gamma activators was evaluated on Reporter gene expression (>25-fold induction). A novel gene regulation system using human PPAR gamma and oral PPAR gamma activators induced reporter gene expression more than 25-fold in rodent skeletal muscle and myocardium.
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