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Gene delivery to the lung using protein/polyethylenimine/plasmid complexes

Gene Therapy volume 9, pages 463–471 (2002)Cite this article

Abstract

Delivery of genes to the lung has enormous potential in a wide variety of illnesses, from lung cancer to genetic deficiency diseases. Many delivery systems have been utilized, each with its own advantages and limitations. Polyethylenimine is a polycation capable of binding and compacting DNA, enabling intravascular plasmid delivery to normal tissues in such a way that the plasmid can be expressed in a proportion of the exposed cells. We have developed a novel intravenous method to deliver small amounts of plasmid to lung tissue, using nontoxic quantities of polyethylenimine in combination with albumin (or other soluble proteins). Injection of 1 μg or less of plasmid resulted in highly efficient gene expression in lung interstitial and endothelial tissues (0.5 to 1 ng luciferase per μg plasmid DNA), while larger quantities of plasmid reduced relative gene expression. Using luciferase as a reporter gene, single injections had maximal gene expression between 24 and 48 h, with a rapid decline thereafter. In contrast to some other delivery systems, however, no inhibition of gene expression occurred during multiple rounds of plasmid administration through 20 days. As a result, this method may have useful applications in diseases that could benefit from recurrent therapeutic gene delivery.

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Acknowledgements

This work was supported by the Department of Veterans Affairs, the Huffington Foundation, the Center for AIDS Research and the Clayton Foundation for Research.

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Authors and Affiliations

  1. Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX, USA

    FM Orson, L Song, BS Bhogal & BM Kinsey

  2. Center for AIDS Research, Baylor College of Medicine, Houston, TX, USA

    FM Orson

  3. Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA

    FM Orson, L Song, BS Bhogal & BM Kinsey

  4. Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX, USA

    FM Orson

  5. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA

    A Gautam & CL Densmore

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  1. FM Orson
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Orson, F., Song, L., Gautam, A. et al. Gene delivery to the lung using protein/polyethylenimine/plasmid complexes. Gene Ther 9, 463–471 (2002). https://doi.org/10.1038/sj.gt.3301666

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