Inflammatory responses following direct injection of plasmid DNA into skeletal muscle (original) (raw)

Gene Therapy volume 5, pages 1283–1290 (1998) Cite this article

Abstract

Transfer of genes by injection of plasmid DNA into skeletal muscle has a wide variety of applications ranging from treatment of neuromuscular disorders to genetic vaccination. We examined each component involved in the intramuscular injection of plasmid DNA in terms of the induction of inflammatory responses. The insertion of a needle and the injection of a relatively large volume of saline caused very little muscle damage except in rare cases. In contrast, barium chloride-induced regeneration of muscle, injection of lipopolysaccharide, plasmid backbone or plasmid expressing a neo-antigen (β-galactosidase) all generated widespread inflammation of injected muscle, with mononuclear infiltrate, comprised largely of macrophages and with both CD4+ and CD8+ T lymphocytes, present. Such inflammation may hamper clinical application of this technology and may encourage undesirable immune responses in gene therapy trials. Inflammation was not greatly reduced by CD4- or CD8-depleting antibodies, suggesting this initial inflammation did not involve T cells, but methylation of plasmid DNA before injection substantially lessened the inflammatory response and resulted in longer term expression of the transgene.

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Authors and Affiliations

  1. Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Gene Targeting Unit, Imperial College School of Medicine, Charing Cross Hospital, St Dunstan’s Road, London, W6 8RP, UK
    JM McMahon, KE Wells, JE Bamfo, MA Cartwright & DJ Wells

Authors

  1. JM McMahon
  2. KE Wells
  3. JE Bamfo
  4. MA Cartwright
  5. DJ Wells

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McMahon, J., Wells, K., Bamfo, J. et al. Inflammatory responses following direct injection of plasmid DNA into skeletal muscle.Gene Ther 5, 1283–1290 (1998). https://doi.org/10.1038/sj.gt.3300718

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