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Enhanced gene transfection of plasmid DNA in the liver with ultrasound and microbubbles

Publication ,  Journal Article
Seip, R; Raju, BI; Leyvi, E; Chin, CT; Li, S; Rouse, C; Koeberl, D; Fodor, W
Published in: Proceedings - IEEE Ultrasonics Symposium
December 1, 2010

Ultrasound mediated delivery (USMD) in the presence of microbubbles is a potentially safe and effective method for gene therapy, offering many desired characteristics such as low toxicity, potential for repeated treatment, as well as organ specificity. In this study we tested the capability of USMD to improve gene transfection to mice livers for treating a rare genetic disorder, Glycogen Storage Disease Type 1a. An image guided therapeutic ultrasound system (TIPS, Philips) was used to provide therapeutic ultrasound to mice liver under IACUC approved protocols. Anesthetized healthy mice were placed supine on a heated pad and coupled to the TIPS transducer. Therapeutic plasmid DNA (FLAG-pG6Pase) was injected and microbubbles infused via the tail vein. Treated animals (n=4) received therapeutic ultrasound pulses (1 MHz, 2.5 MPa) over the entire liver. Control animals (n=5) received pDNA but not ultrasound treatment. Post treatment the animals were left to recover and subsequently sacrificed after 5 days. Tissues from the left, middle, caudal, right anterior, and right posterior liver lobes were harvested and stored. Quantitative PCR assays were then performed on the samples to quantify gene transfection. Ultrasound treated animals showed significantly higher levels of G6Pase transfection compared to control animals (p>0.05) in all five lobes of the liver. On average, the treated animals showed 5.4 times more pDNA accumulation in the liver compared to controls. Immunohistochemistry staining for FLAG tag showed increased transgene expression especially around the blood vessels in treated animals. No evidence of toxicity was found up to 5 days post treatment. © 2010 IEEE.

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Published In

Proceedings - IEEE Ultrasonics Symposium

DOI

ISSN

1051-0117

Publication Date

December 1, 2010

Start / End Page

103 / 106
 

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Seip, R., Raju, B. I., Leyvi, E., Chin, C. T., Li, S., Rouse, C., … Fodor, W. (2010). Enhanced gene transfection of plasmid DNA in the liver with ultrasound and microbubbles. Proceedings - IEEE Ultrasonics Symposium, 103–106. https://doi.org/10.1109/ULTSYM.2010.5935589
Seip, R., B. I. Raju, E. Leyvi, C. T. Chin, S. Li, C. Rouse, D. Koeberl, and W. Fodor. “Enhanced gene transfection of plasmid DNA in the liver with ultrasound and microbubbles.” Proceedings - IEEE Ultrasonics Symposium, December 1, 2010, 103–6. https://doi.org/10.1109/ULTSYM.2010.5935589.
Seip R, Raju BI, Leyvi E, Chin CT, Li S, Rouse C, et al. Enhanced gene transfection of plasmid DNA in the liver with ultrasound and microbubbles. Proceedings - IEEE Ultrasonics Symposium. 2010 Dec 1;103–6.
Seip, R., et al. “Enhanced gene transfection of plasmid DNA in the liver with ultrasound and microbubbles.” Proceedings - IEEE Ultrasonics Symposium, Dec. 2010, pp. 103–06. Scopus, doi:10.1109/ULTSYM.2010.5935589.
Seip R, Raju BI, Leyvi E, Chin CT, Li S, Rouse C, Koeberl D, Fodor W. Enhanced gene transfection of plasmid DNA in the liver with ultrasound and microbubbles. Proceedings - IEEE Ultrasonics Symposium. 2010 Dec 1;103–106.

Published In

Proceedings - IEEE Ultrasonics Symposium

DOI

ISSN

1051-0117

Publication Date

December 1, 2010

Start / End Page

103 / 106