title: On the feasibility of MRI-guided focused ultrasound for local induction of gene expression.
abstract: 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.
authors.affiliation: In Vivo NMR Research Center, BEIP, NCRR, National Institutes of Health, Bethesda, MD 20892-1060, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Madio
authors.forename: P
authors.initials: P
authors.lastname: van Gelderen
authors.forename: D
authors.initials: D
authors.lastname: DesPres
authors.forename: A W
authors.initials: AW
authors.lastname: Olson
authors.forename: J A
authors.initials: JA
authors.lastname: de Zwart
authors.forename: T W
authors.initials: TW
authors.lastname: Fawcett
authors.forename: N J
authors.initials: NJ
authors.lastname: Holbrook
authors.forename: M
authors.initials: M
authors.lastname: Mandel
authors.forename: C T
authors.initials: CT
authors.lastname: Moonen
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D005240:Feasibility Studies; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006614:Hindlimb; D008279:Magnetic Resonance Imaging; D018482:Muscle, Skeletal / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014464:Ultrasonic Therapy
chemical_list: D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger