MRI-guided ultrasonic heating allows spatial control of exogenous luciferase in canine prostate.
The need for efficient and controlled delivery is one of the major obstacles to clinical use of gene therapy. In this study, we investigated the use of magnetic resonance imaging-monitored ultrasound (US) to induce expression of luciferase after local injection of the construct Ad-HSP-Luc, an adenoviral vector containing a transgene encoding firefly luciferase under the control of the human hsp70B promoter. The hsp promoter allows induction of the associated transgene only in areas that are subsequently heated after infection. US imaging was used to guide the injection of purified virus into both lobes of the prostates of three beagles. At 48 h after injection, the left lobe of the prostate was heated using a 1.5-MHz US transducer driven by a multichannel radiofrequency system and employing an magnetic resonance imaging guidance system. High levels of luciferase expression were observed only in areas exposed to ultrasonic heating. This study demonstrates the feasibility of using ultrasonic heating to control transgene expression spatially using a minimally-invasive approach.
Brigham & Women's Hospital/Harvard Medical School, Boston, MA 02115, USA. csilcox@mit.edu
Christina E
CE
Silcox
Roy C
RC
Smith
Randy
R
King
Nathan
N
McDannold
Peter
P
Bromley
Kenneth
K
Walsh
Kullervo
K
Hynynen
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004285:Dogs; D005240:Feasibility Studies; D005786:Gene Expression Regulation; D018390:Gene Targeting / Q000379:methods; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006979:Hyperthermia, Induced; D008156:Luciferases / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D011467:Prostate / Q000201:enzymology*; D019076:Transgenes; D014464:Ultrasonic Therapy / Q000379:methods*
D018840:HSP70 Heat-Shock Proteins; C491129:HSPA7 protein, human; D008156:Luciferases