In vivo gene regulation using tetracycline-regulatable systems.
Numerous preclinical studies have demonstrated the efficacy of viral gene delivery vectors, and recent clinical trials have shown promising results. However, the tight control of transgene expression is likely to be required for therapeutic applications and in some instances, for safety reasons. For this purpose, several ligand-dependent transcription regulatory systems have been developed. Among these, the tetracycline-regulatable system is by far the most frequently used and the most advanced towards gene therapy trials. This review will focus on this system and will describe the most recent progress in the regulation of transgene expression in various organs, including the muscle, the retina and the brain. Since the development of an immune response to the transactivator was observed following gene transfer in the muscle of nonhuman primate, focus will be therefore, given on the immune response to transgene products of the tetracycline inducible promoter.
Stieger
Knut
K
INSERM UMR U649, CHU-Hotel Dieu, Nantes, France.
Belbellaa
Brahim
B
Le Guiner
Caroline
C
Moullier
Philippe
P
Rolling
Fabienne
F
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D011323:Primates; D013752:Tetracycline / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000235:genetics; D019076:Transgenes / Q000187:drug effects
D000900:Anti-Bacterial Agents; D013752:Tetracycline