Abstract
Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier can, in part, be overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine using either a cationic lipid or a cationic polymer as the gene transfer agent. Further, in vivo application of either Nacystelyn or the anticholinergic glycopyrrolate, both clinically used agents, resulted in increased reporter gene expression in the mouse lung, but no significant correction of the bioelectric defect in CF null mice. These results, whilst unlikely to be sufficient in themselves to achieve clinically relevant gene therapy, may be a further useful step in the attainment of this goal. Gene Therapy (2001) 8, 1380–1386.
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Acknowledgements
We would like to thank Tony Phillips for his support and discussions, Karen Palin and Mike Holton for logistics and supply of the EDMPC:Chol complexes. L-PEI was kindly provided by Prof JP Behr (Université L Pasteur, Illkirch, France). SF was supported by a CF Trust Fellowship, EWFWA by Wellcome Trust Senior Clinical Fellowship and the studies by the Cystic Fibrosis Research Trust.
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Ferrari, S., Kitson, C., Farley, R. et al. Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium. Gene Ther 8, 1380–1386 (2001). https://doi.org/10.1038/sj.gt.3301525
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DOI: https://doi.org/10.1038/sj.gt.3301525
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