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  • Nonviral Transfer Technology
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Liposome-mediated, nonviral gene transfer induces a systemic inflammatory response which can exacerbate pre-existing inflammation

Gene Therapy volume 7, pages 1425–1430 (2000)Cite this article

Abstract

Cationic liposome and plasmid-mediated gene transfer has emerged as a novel technique for the targeted delivery of protein-based therapies in acute inflammatory diseases. However, concerns have arisen that cationic liposomes and plasmid DNA have inherent proinflammatory properties which could exacerbate pre-existing inflammatory processes. In healthy mice, intraperitoneal administration of cationic liposomes (200 nmol) complexed to plasmid DNA (100 μg) induced a proinflammatory response characterized by the induction of tumor necrosis factor α and interleukin-1β mRNA expression. The plasma concentrations of the hepatic acute phase proteins interleukin-6, amyloid A, amyloid P, and seromucoid were also increased (P < 0.05), and this response was seen in endotoxin-resistant (c3h/hej) mice. the inflammatory response associated with gene transfer increased the mortality and severity of experimentally induced sterile inflammation (pancreatitis). we conclude that systemic administration of cationic liposomes and plasmid dna is associated with induction of the innate immune response which may exacerbate pre-existing inflammatory processes.

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Acknowledgements

This work was supported in part by a VA Merit Review Grant (JN), and GM-52532 and GM-40586 (to LLM) awarded by the National Institute of General Medical Services.

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Authors and Affiliations

  1. Department of Surgery, University of South Florida College of Medicine, Tampa, USA

    J Norman, W Denham, D Denham, J Yang & G Carter

  2. Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

    A Abouhamze, CL Tannahill, SLD MacKay & LL Moldawer

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  1. J Norman
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  2. W Denham
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Norman, J., Denham, W., Denham, D. et al. Liposome-mediated, nonviral gene transfer induces a systemic inflammatory response which can exacerbate pre-existing inflammation. Gene Ther 7, 1425–1430 (2000). https://doi.org/10.1038/sj.gt.3301240

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