On the feasibility of MRI-guided focused ultrasound for local induction of gene expression

Gene therapy is a promising approach to the treatment of many forms of disease, including cancer. Of critical concern in its implementation is the ability to control the location, duration, and level of expression of the therapeutic gene. Here, we propose the use of local heat in combination with a...

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Bibliographic Details
Published inJournal of magnetic resonance imaging Vol. 8; no. 1; p. 101
Main Authors Madio, D P, van Gelderen, P, DesPres, D, Olson, A W, de Zwart, J A, Fawcett, T W, Holbrook, N J, Mandel, M, Moonen, C T
Format Journal Article
LanguageEnglish
Published United States 01.01.1998
Subjects
Animals
Blotting, Northern
Feasibility Studies
Gene Expression
Genetic Therapy - methods
Hindlimb
HSP70 Heat-Shock Proteins - biosynthesis
Magnetic Resonance Imaging
Muscle, Skeletal - metabolism
Rats
Rats, Sprague-Dawley
RNA, Messenger - genetics
Ultrasonic Therapy
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Summary:Gene therapy is a promising approach to the treatment of many forms of disease, including cancer. Of critical concern in its implementation is the ability to control the location, duration, and level of expression of the therapeutic gene. Here, we propose the use of local heat in combination with a heat-sensitive promoter to help accomplish this. Certain members of the family of heat shock protein (hsp) promoters display a regulation that depends strongly on temperature. We present a study of natural hsp70 induction in rat leg by MRI-guided focused ultrasound to investigate the hsp70 promoter as a possible candidate for use in control of gene expression with local heat. A temperature increase of 5-8 degrees C in the focal region for 45 minutes led to a differential expression of the hsp70 mRNA between the focal region and the surrounding tissue ranging from a factor of 3 to 67.
ISSN:1053-1807
DOI:10.1002/jmri.1880080120