Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents

We have evaluated if ultrasound imaging (US) and various commercially available contrast microbubbles can serve as a non‐invasive systemically administered delivery vehicle for site‐specific adenoviral‐mediated gene transfer in vitro and in vivo. The contrast agents were tested for their ability to...

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Bibliographic Details
Published in:Journal of cellular physiology 2006-11, Vol.209 (2), p.413-421
Main Authors: Howard, Candace M., Forsberg, Flemming, Minimo, Corrado, Liu, Ji-Bin, Merton, Daniel A., Claudio, Pier Paolo
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adsorption
Animals
Complement System Proteins - immunology
Contrast Media - metabolism
Female
Fluorescence
Gene Transfer Techniques
Genetic Vectors - metabolism
Green Fluorescent Proteins - metabolism
Humans
Melanoma - pathology
Mice
Mice, Nude
Microbubbles
Transplantation, Heterologous
Tumor Cells, Cultured
Ultrasonics
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Summary:We have evaluated if ultrasound imaging (US) and various commercially available contrast microbubbles can serve as a non‐invasive systemically administered delivery vehicle for site‐specific adenoviral‐mediated gene transfer in vitro and in vivo. The contrast agents were tested for their ability to enclose and to protect an adenoviral vector carrying the GFP marker gene (Ad‐GFP) into the microbubbles. We have also evaluated the ability of the innate immune system to inactivate free adenoviruses as well as unenclosed viruses adsorbed on the surface of the contrast agents and in turn the ability of the microbubbles to enclose and to protect the viral vectors from such agents. In vitro as well as in vivo, innate components of the immune system were able to serve as inactivating agents to clear free viral particles and unenclosed adenoviruses adsorbed on the microbubbles' surface. Systemic delivery of Ad‐GFP enclosed into microbubbles in the tail vein of nude mice resulted in specific targeting of the GFP transgene. Both fluorescence microscopy and GFP immunohistochemistry demonstrated US guided specific transduction in the targeted cells only, with no uptake in either heart, lungs or liver using complement‐pretreated Ad‐GFP microbubbles. This approach enhances target specificity of US microbubble destruction as a delivery vehicle for viral‐mediated gene transfer. J. Cell. Physiol. 209: 413–421, 2006. © 2006 Wiley‐Liss, Inc.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.20736