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

Gene therapy is a promising approach to the treatment of many forms of dise ase, including cancer. Of critical concern in its implementation is the abi lity to control the location, duration, and level of expression of the ther apeutic gene. Here, we propose the use of local heat in combination with a heat-sensitive promoter to help accomplish this. Certain members of the fam ily 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 he at. A temperature increase of 5-8 degrees C in the focal region for 45 minu tes led to a differential expression of the hsp70 mRNA between the focal re gion and the surrounding tissue ranging from a factor of 3 to 67.