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Cationic lipid-mediated gene transfer to the growing murine and human airway

Gene Therapy volume 7, pages 273–278 (2000)Cite this article

Abstract

Gene therapy in patients with cystic fibrosis may need to be commenced before the onset of lung disease which may be evident as early as 4 weeks after birth. We assessed the efficacy of cationic lipid-mediated transfer of a reporter gene, chloramphenicol acetyltransferase, in the growing murine and human respiratory tract. Gene expression was greater in adult mice (greater than 8 weeks old) compared with 9- and 16-day-old animals, despite a relatively greater proportion of complex delivered to the younger mice. Subsequent experiments compared 16-day-old and adult mice. Whilst higher gene expression occurred in the parenchyma compared with conducting airways in both groups, significantly greater expression was seen in the conducting airway of adult mice compared with 16-day-old animals. This expression persisted beyond 18 days in the adults but was undetectable in the younger group at this time-point. In an ex vivo model there was no difference in gene expression between the two groups. Further, no differences were observed in gene expression between growing (age 5 weeks to 14 years 8 months) and adult human lung tissue in either parenchyma or conducting airway. These data suggest age-dependent differences in gene transfer in vivo, which are not seen in an ex vivo setting. Proof-of-principle has been demonstrated for cationic-lipid mediated gene transfer to the growing human lung.

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Acknowledgements

We would like to thank Mr P Goldstraw, Mr M Petrou, Mr M Elliott, Mr G Laddas, Dr M Malone and Dr A Wilkinson for supplying the human tissue used. The study was sponsored by the Cystic Fibrosis Research Trust, the Van Heyningen Family and a Wellcome Trust Senior Clinical Fellowship (EWFWA).

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Authors and Affiliations

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

    A Jaffé, D Judd, D M Geddes & E W F W Alton

  2. Department of Respiratory Paediatrics, Royal Brompton and Harefield NHS Trust, London, UK

    A Jaffé & A Bush

  3. Department of Thoracic Surgery, Royal Brompton and Harefield NHS Trust, London, UK

    C Ratcliffe

  4. Genzyme Corporation, Framingham, MA, USA

    S H Cheng

Authors
  1. A Jaffé
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  2. D Judd
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  3. C Ratcliffe
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  4. S H Cheng
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  5. A Bush
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  6. D M Geddes
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  7. E W F W Alton
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Jaffé, A., Judd, D., Ratcliffe, C. et al. Cationic lipid-mediated gene transfer to the growing murine and human airway. Gene Ther 7, 273–278 (2000). https://doi.org/10.1038/sj.gt.3301091

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