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  • Nonviral Transfer Technology
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Microbubble-enhanced ultrasound for vascular gene delivery

Gene Therapy volume 7, pages 2023–2027 (2000)Cite this article

Abstract

Progress in cardiovascular gene therapy has been hampered by concerns over the safety and practicality of viral vectors and the inefficiency of current nonviral transfection techniques. We have previously reported that ultrasound exposure (USE) enhances transgene expression in vascular cells by up to 10-fold after naked DNA transfection, and enhances lipofection by up to three-fold. We report here that performing USE in the presence of microbubble echocontrast agents enhances acoustic cavitation and is associated with approximately 300-fold increments in transgene expression after naked DNA transfections. This approach also enhances by four-fold the efficiency of polyplex transfection, yielding transgene expression levels approximately 3000-fold higher than after naked DNA alone. These data indicate an important role for acoustic cavitation in the effects of USE. Ultrasound can be focused upon almost any organ and hence this approach holds promise as a means to deliver targeted gene therapy in cardiovascular conditions such as such angioplasty restenosis and in many other clinical situations.

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Acknowledgements

This study was supported by a project grant (PG/98139) from the British Heart Foundation. Ultrasound equipment and expertise was provided by PharmaSonics Inc.

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Authors and Affiliations

  1. Division of Clinical Sciences, Cardiovascular Research Group, University of Sheffield, Sheffield, UK

    A Lawrie, SE Francis, DC Cumberland, DC Crossman & CM Newman

  2. PharmaSonics Inc., Sunnyvale, CA, USA

    AF Brisken

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  1. A Lawrie
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  2. AF Brisken
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  3. SE Francis
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  4. DC Cumberland
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Lawrie, A., Brisken, A., Francis, S. et al. Microbubble-enhanced ultrasound for vascular gene delivery. Gene Ther 7, 2023–2027 (2000). https://doi.org/10.1038/sj.gt.3301339

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