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Effects of altering dosing on cationic liposome-mediated gene transfer to the respiratory epithelium

Gene Therapy volume 6, pages 1313–1316 (1999)Cite this article

Abstract

Liposome-mediated gene transfer is currently sub-optimal with respect to both the extent and duration of transgene expression. We investigated whether simple changes in DNA dosing could enhance either of these outcomes. Increasing DNA doses produced highest transgene expression at an intermediate dose with toxicity observed at higher doses, thereby likely limiting expression. Adminis- tering an equivalent DNA dose in aliquots over a 1–3 day period resulted in significantly lower gene expression and did not increase the duration of expression. Administration at different times of the day (and hence wake/sleep cycles of the animals) did not alter gene expression. We conclude that such simple changes in dosing regimes are unlikely to contribute to improvements in gene transfer efficiency.

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Acknowledgements

The study was supported by the Cystic Fibrosis Research Trust and by a Wellcome Trust Senior Clinical Fellowship (EWFWA).

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Authors and Affiliations

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

    E Hillery, D M Geddes & E W F W Alton

  2. Genzyme Corporation, Framingham, MA, USA

    S H Cheng

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  1. E Hillery
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  3. D M Geddes
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  4. E W F W Alton
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Hillery, E., Cheng, S., Geddes, D. et al. Effects of altering dosing on cationic liposome-mediated gene transfer to the respiratory epithelium. Gene Ther 6, 1313–1316 (1999). https://doi.org/10.1038/sj.gt.3300953

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  • DOI: https://doi.org/10.1038/sj.gt.3300953

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