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Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice

Gene Therapy volume 19, pages 877–885 (2012)Cite this article

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Abstract

Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcγ receptor–Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16AF-Ig, CD32AR-Ig and CD32AH-Ig) reached a maximum of 130 μg ml–1 of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcγR-Igs was found to be 9–16 days and western blot analysis showed that the FcγR-Igs were expressed as a homodimer. The hydrodynamically expressed FcγR-Igs blocked 50–80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcγR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcγR-Ig gene can be used to study the consequences of blocking IC binding to FcγRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.

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Acknowledgements

This study was supported by the NIH Grants R21HL09126802 and R21AR05682101 to PS and the AHA grant 11SDG5710004 to RS. We also thank Ms Archana Boopathy, Ms Sumi Selvaraj and Ms Danielle Daniels for critical reading of the article.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    R Shashidharamurthy, D Machiah, E N Bozeman, S Srivatsan, J Patel, A Cho, J Jacob & P Selvaraj

  2. Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic Medicine, School of Pharmacy, Suwaneek, GA-30024, USA

    R Shashidharamurthy

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  1. R Shashidharamurthy
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Correspondence to P Selvaraj.

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Shashidharamurthy, R., Machiah, D., Bozeman, E. et al. Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice. Gene Ther 19, 877–885 (2012). https://doi.org/10.1038/gt.2011.175

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