Image-guided, noninvasive, spatiotemporal control of gene expression.
Spatiotemporal control of transgene expression is of paramount importance in gene therapy. Here, we demonstrate the use of magnetic resonance temperature imaging (MRI)-guided, high-intensity focused ultrasound (HIFU) in combination with a heat-inducible promoter [heat shock protein 70 (HSP70)] for the in vivo spatiotemporal control of transgene activation. Local gene activation induced by moderate hyperthermia in a transgenic mouse expressing luciferase under the control of the HSP70 promoter showed a high similarity between the local temperature distribution in vivo and the region emitting light. Modulation of gene expression is possible by changing temperature, duration, and location of regional heating. Mild heating protocols (2 min at 43 degrees C) causing no tissue damage were sufficient for significant gene activation. The HSP70 promoter was shown to be induced by the local temperature increase and not by the mechanical effects of ultrasound. Therefore, the combination of MRI-guided HIFU heating and transgenes under control of heat-inducible HSP promoter provides a direct, noninvasive, spatial control of gene expression via local hyperthermia.
Deckers
Roel
R
Laboratory for Molecular and Functional Imaging: From Physiology to Therapy, Unité Mixte de Recherche 5231, Centre National de la Recherche Scientifique/University Victor Segalen Bordeaux, 146 Rue Leo Saignat, Case 117, 33076 Bordeaux, France.
Quesson
Bruno
B
Arsaut
Josette
J
Eimer
Sandrine
S
Couillaud
Franck
F
Moonen
Chrit T W
CT
D000818:Animals; D001833:Body Temperature Regulation; D001854:Bone Marrow Cells / Q000378:metabolism; D005121:Extremities; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D018869:Heat-Shock Response / Q000235:genetics; D007700:Kinetics; D008027:Light; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D013997:Time Factors; D014465:Ultrasonics; D051598:Whole Body Imaging
D018840:HSP70 Heat-Shock Proteins