Regulatable gene expression systems for gene therapy.
It is feasible to restrict transgene expression to a tissue or region in need of therapy by using promoters that respond to focusable physical stimuli. The most extensively investigated promoters of this type are radiation-inducible promoters and heat shock protein gene promoters that can be activated by directed, transient heat. Temporal regulation of transgenes can be achieved by various two- or three-component gene switches that are triggered by an appropriate small molecule inducer. The most commonly considered gene switches that are reviewed herein are based on small molecule-responsive transactivators derived from bacterial tetracycline repressor, insect or mammalian steroid receptors, or mammalian FKBP12/FRAP. A new generation of gene switches combines a heat shock protein gene promoter and a small molecule-responsive gene switch and can provide for both spatial and temporal regulation of transgene activity.
Vilaboa
Nuria
N
Unidad de Investigación, Hospital Universitario La Paz, Madrid, Spain.
Voellmy
Richard
R
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D018390:Gene Targeting; D015316:Genetic Therapy; D006801:Humans