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Pegylated GL67 lipoplexes retain their gene transfection activity after exposure to components of CF mucus

Gene Therapy volume 9, pages 363–371 (2002)Cite this article

Abstract

The highly viscous secretions lining the upper airways and bronchi of cystic fibrosis (CF) patients may pose a significant barrier to successful gene therapy of the lung. In this report we examined the influence of CF mucus components (albumin, DNA, mucin and phospholipids) on the gene transfection activity of cationic DOTAP-based lipoplexes and pegylated GL67-based lipoplexes which previously have been used in CF clinical studies. Upon exposure of the cationic DOTAP:DOPE lipoplexes to either albumin, linear DNA or mucin (at concentration ratios expected to occur in vivo) a significant decrease in gene transfection activity was observed. This was primarily due to aggregation of the lipoplexes. However, exposure of pegylated GL67 lipoplexes to the same components did not affect their gene transfection activity. Indeed, it was determined that CF mucus components did not interact significantly with these pegylated GL67 lipoplexes. These results suggest that charge shielding of cationic gene carriers with pEG may favor their physicochemical stability in CF mucus and thereby aid in preserving their transfection activity.

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Acknowledgements

Niek Sanders is a doctoral fellow of IWT. The financial support of this institute is acknowledged with gratitude. Ghent University (BOF) is acknowledged for their support through instrumentation credits. FWO is acknowledged for their financial support to this project (grant G.0310.02). The pDNA was a gift from Prof Tavernier (Ghent University) and the Cos1 cells were obtained from Geritt Borchard (University of Leiden). We also want to thank Kris De Vriendt, Tineke Van Hooland and Annelore Vandeputte for their excellent assistance.

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Authors and Affiliations

  1. Faculty of Pharmacy, Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium

    NN Sanders, SC De Smedt & J Demeester

  2. Genzyme Corporation, Framingham, MA, USA

    SH Cheng

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  1. NN Sanders
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  2. SC De Smedt
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Sanders, N., De Smedt, S., Cheng, S. et al. Pegylated GL67 lipoplexes retain their gene transfection activity after exposure to components of CF mucus. Gene Ther 9, 363–371 (2002). https://doi.org/10.1038/sj.gt.3301663

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