Spatial and temporal control of transgene expression in vivo using a heat‐sensitive promoter and MRI‐guided focused ultrasound
2003
Background
Among the techniques used to induce and control gene expression, a non-invasive, physical approach based on local heat in combination with a heat-sensitive promoter represents a promising alternative but requires accurate temperature control in vivo. MRI-guided focused ultrasound (MRI-FUS) with real-time feedback control allows automatic execution of a predefined temperature-time trajectory. The purpose of this study was to demonstrate temporal and spatial control of transgene expression based on a well-defined local hyperthermia generated by MRI-FUS.
Methods
Expression of the green fluorescent protein (GFP) marker gene was used. Two cell lines were derived from C6 glioma cells. The GFP expression of the first one is under the control of the CMV promoter, whereas it is under the control of the HSP70 promoter in the second one and thus inducible by heat. Subcutaneous tumours were generated by injection in immuno-deficient mice and rats. Tumours were subjected to temperatures varying from 42 to 50 °C for 3 to 25 min controlled by MRI-FUS and analyzed 24 h after the heat-shock. Endogenous HSP70 expression and C6 cell distribution were also analyzed.
Results
The results demonstrate strong expression at 50 °C applied during a short time period (3 min) without affecting cell viability. Induced expression was also clearly shown for temperature in the range 44–48 °C but not at 42 °C.
Conclusions
Heating with MRI-FUS allows a tight and non-invasive control of transgene expression in a tumour. Copyright © 2002 John Wiley & Sons, Ltd.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
49
References
72
Citations
NaN
KQI