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Use of ultrasound to enhance nonviral lung gene transfer in vivo

Gene Therapy volume 14, pages 768–774 (2007)Cite this article

Abstract

We have assessed if high-frequency ultrasound (US) can enhance nonviral gene transfer to the mouse lung. Cationic lipid GL67/pDNA, polyethylenimine (PEI)/pDNA and naked plasmid DNA (pDNA) were delivered via intranasal instillation, mixed with Optison microbubbles, and the animals were then exposed to 1 MHz US. Addition of Optison alone significantly reduced the transfection efficiency of all three gene transfer agents. US exposure did not increase GL67/pDNA or PEI/pDNA gene transfer compared to Optison-treated animals. However, it increased naked pDNA transfection efficiency by approximately 15-fold compared to Optison-treated animals, suggesting that despite ultrasound being attenuated by air in the lung, sufficient energy penetrates the tissue to increase gene transfer. US-induced lung haemorrhage, assessed histologically, increased with prolonged US exposure. The left lung was more affected than the right and this was mirrored by a lesser increase in naked pDNA gene transfer, in the left lung. The positive effect of US was dependent on Optison, as in its absence US did not increase naked pDNA transfection efficiency. We have thus established proof of principle that US can increase nonviral gene transfer, in the air-filled murine lung.

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Acknowledgements

This work was supported by UK Cystic Fibrosis Trust, through a grant to the UK Cystic Fibrosis Gene Therapy Consortium.

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Authors and Affiliations

  1. Department of Gene Therapy, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK

    S Xenariou, U Griesenbach, J Zhu, R Farley, L Somerton, C Singh, P K Jeffery, S Ferrari, D M Geddes & E W F W Alton

  2. UK Cystic Fibrosis Gene Therapy Consortium, London, UK

    S Xenariou, U Griesenbach, R Farley, L Somerton, C Singh, S Ferrari, D M Geddes & E W F W Alton

  3. Imaging Sciences Department, Ultrasound Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, UK

    H-D Liang & M Blomley

  4. School of Engineering, University of Cardiff, Cardiff, UK

    H-D Liang

  5. Genzyme Corporation, Framingham, MA, USA

    R K Scheule & S H Cheng

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  1. S Xenariou
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Correspondence to U Griesenbach.

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Xenariou, S., Griesenbach, U., Liang, HD. et al. Use of ultrasound to enhance nonviral lung gene transfer in vivo. Gene Ther 14, 768–774 (2007). https://doi.org/10.1038/sj.gt.3302922

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