Image-guided, Noninvasive, Spatiotemporal Control of Gene Expression

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 Jan 24

PMID 19164593

Citations 36

Authors

Roel Deckers

Bruno Quesson

Josette Arsaut

Sandrine Eimer

Franck Couillaud

Chrit T W Moonen

Affiliations

Soon will be listed here.

Abstract

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.

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