Focused ultrasound helps exogenous genes permeate targeted cells' outer membrane


CONTEXT: National Institutes of Health researchers have successfully broken through the cell membrane, a barrier that has frustrated the efforts of many gene therapy strategies. Their study, published in the May 2005 issue of Radiology, found that high-intensity focused ultrasound significantly increases the number of exogenous genes that permeate the cells of subcutaneous squamous cell carcinomas. Ultrasonic waves were delivered in short pulses to dissipate heat and generate mechanical power that increased a tumor cell's permeability by therapeutic genes.

RESULTS: Under the guidance of Dr. King C.P. Li, Dr. Kristin Dittmar and colleagues in the diagnostic imaging department of the NIH Clinical Center applied ultrasonic waves to one of two tumors growing on both flanks of mice, which immediately received injections of the reporter gene encoded for fluorescent green protein. Fluorescence microscopy detected green fluorescent protein exclusively in tumors that received exposure to the ultrasound. Western blot analysis revealed that the ultrasound-exposed cells emitted fluorescent signals nine times more intense than signals from cells in the tumors that did not receive ultrasound.

IMAGES: Stained histologic sections reveal the nuclei of tumor cells in blue as seen with fluorescence microscopy. Green fluorescent protein reporter gene expression was not seen in control tumor that was not exposed to pulsed ultrasound (A) but does appear in green in a tumor exposed to pulsed ultrasound (B).

IMPLICATIONS: This procedure is hypothetically generic for enhancing delivery to all tissues, according to coauthor Victor Frenkel, Ph.D. Li previously demonstrated that tumor cells increase their uptake of chemotherapeutic drugs with a similar ultrasound treatment.

"Now we've shown that it works for genes, and we're making the case that there's a connection between the two," Frenkel said.

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